Covid19
Conditions
Keywords
SARS-CoV-2, coronavirus, coronavirus disease 2019, COVID-19
Brief summary
This is a phase 2/3 study in which subjects with coronavirus disease 2019 (COVID-19) will receive VIR-7831 or placebo and will be assessed for safety, tolerability, efficacy, and pharmacokinetics.
Interventions
BIOLOGICALVIR-7831 (sotrovimab)
VIR-7831 (sotrovimab) given by intravenous infusion (single dose)
DRUGPlacebo
Sterile normal saline (0.9% NaCl) given by intravenous infusion (single dose)
Sponsors
GlaxoSmithKline
Vir Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must be aged 18 years or older AND at high risk of progression of COVID-19 or ≥ 55 years old * Participants must have a positive SARS-CoV-2 test result and oxygen saturation ≥94% on room air and have COVID-19 symptoms and be less than or equal to 5 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Had Progression of COVID-19 Through Day 29 | Through Day 29 | COVID-19 progression defined as hospitalization \>24 hours or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs) | Up to 24 weeks | — |
| Number of Participants With Infusion-related Reactions (IRR) Including Hypersensitivity Reactions | Up to 24 weeks | — |
| Number of Participants With Cardiac Events of Special Interest | Up to 24 weeks | — |
| Number of Participants With Serum Anti-drug Antibody (ADA) to Sotrovimab | Up to 24 weeks | — |
| Titers of Serum Anti-drug Antibody (ADA) to Sotrovimab | Up to 24 Weeks | Titers defined as the reciprocal of the highest dilution of the sample (including minimum required dilution) that yields a positive result. |
| Maximum Observed Concentration (Cmax) of VIR-7831 After IV Administration | Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169 | — |
| Concentration at the Last Quantifiable Time Point (Clast) of VIR-7831 After IV Administration | Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169 | — |
| Time to Reach the Maximum Concentration (Tmax) of VIR-7831 After IV Administration | Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169 | — |
| Time of the Last Quantifiable Concentration (Tlast) of VIR-7831 After IV Administration | Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169 | — |
| Area Under the Serum Concentration-time Curve Extrapolated From Zero to Infinity (AUCinf) of VIR-7831 After IV Administration | Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169 | — |
| Area Under the Serum Concentration-time Curve From the Time of Dosing to the Time of the Last Measurable (Positive) Concentration (AUClast) of VIR-7831 After IV Administration | Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169 | — |
| Percentage of AUCinf Obtained by Extrapolation (%AUCexp) for VIR-7831 After IV Administration | Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169 | — |
| Terminal Elimination Half-life (t1/2) of VIR-7831 After IV Administration | Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169 | — |
| Number of Participants With Adverse Events (AEs) | Up to 24 weeks | — |
| Apparent Volume of Distribution at Steady State (Vss) of VIR-7831 Following IV Administration | Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169 | — |
| Clearance (CL) of VIR-7831 After IV Administration | Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169 | — |
| Number of Participants Who Had Progression of COVID-19 | Through Day 29 | COVID-19 progression defined as a visit to a hospital emergency room for management of illness or hospitalization for acute management of illness or death |
| Mean Change in FLU PRO Plus Total Score (AUC) | Through Day 7 | Mean change in InFLUenza Patient-Reported Outcome (FLU-PRO Plus) questionnaire total score. The FLU-PRO is a 32-item daily diary assessing influenza symptoms and severity across 6 body systems (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic). The FLU-PRO Plus includes the 32-item FLU-PRO with 2 additional items for loss of smell and taste. The mean total score can range from 0 (symptom free) to 4 (very severe symptoms) and was calculated as the arithmetic mean of the 32 items within FLU-PRO. Missing total score at day 7 was imputed using a modified last observation carried forward approach. |
| Time to Symptom Alleviation Using FLU-PRO Plus | Through Day 21 | Symptom alleviation is defined as absence of the majority of core symptoms of COVID-19 (except for cough or fatigue, where scoring no more than 'somewhat' in severity, and loss of smell or taste were allowed) as measured by FLU-PRO Plus, sustained for \>=48 hours. Participants could only achieve sustained symptom alleviation following \>=2 non-missing consecutively scored questionnaires that showed symptom alleviation. Participants who did not achieve sustained symptom alleviation were censored at Day 21, the day of death, or the day of withdrawal, whichever was earliest. Days where symptom alleviation could not be assessed to a missing/incomplete questionnaire were imputed as no symptom alleviation. The FLU-PRO is a 32-item daily diary assessing influenza symptoms and severity across 6 body systems (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic). The FLU-PRO Plus includes the 32-item FLU-PRO with 2 additional items for loss of smell and taste. |
| Change From Baseline in Viral Load in Nasal Secretions by qRT-PCR at Day 8 | Baseline and Day 8 | — |
| Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 8 | Through Day 8 | — |
| Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 15 | Through Day 15 | Participants were defined as progression to severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progression to critical respiratory COVID-19 if they required invasive mechanical ventilation or ECMO. |
| Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 22 | Through Day 22 | Participants were defined as progression to severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progression to critical respiratory COVID-19 if they required invasive mechanical ventilation or ECMO. |
| Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 29 | Through Day 29 | Participants were defined as progression to severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progression to critical respiratory COVID-19 if they required invasive mechanical ventilation or ECMO. |
| 29-day All-cause Mortality | Through Day 29 | Participants alive at the respective follow-up timepoint were censored at that timepoint; participants who withdrew prior to the respective timepoint were censored at the time of study withdrawal |
| 60-day All-cause Mortality | Through Day 60 | Participants alive at the respective follow-up timepoint were censored at that timepoint; participants who withdrew prior to the respective timepoint were censored at the time of study withdrawal |
| 90-day All-cause Mortality | Through Day 90 | Participants alive at the respective follow-up timepoint were censored at that timepoint; participants who withdrew prior to the respective timepoint were censored at the time of study withdrawal |
| Apparent Volume of Distribution During the Elimination Phase (Vz) of VIR-7831 Following IV Administration | Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169 | — |
Countries
Austria, Brazil, Canada, Peru, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
The study comprised two parts: lead-in phase and expansion phase
Participants by arm
| Arm | Count |
|---|---|
| Sotrovimab (500 mg IV) Participants received 500 mg sotrovimab administered intravenously (IV) | 528 |
| Placebo Participants received placebo administered intravenously (IV) | 529 |
| Total | 1,057 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 0 | 5 |
| Overall Study | Lost to Follow-up | 10 | 13 |
| Overall Study | Physician Decision | 3 | 0 |
| Overall Study | Withdrawal by Subject | 17 | 22 |
Baseline characteristics
| Characteristic | Sotrovimab (500 mg IV) | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 6 Participants | 4 Participants |
| Age, Categorical >=65 years | 105 Participants | 213 Participants | 108 Participants |
| Age, Categorical Between 18 and 65 years | 421 Participants | 838 Participants | 417 Participants |
| Age, Continuous | 51.6 years STANDARD_DEVIATION 15.07 | 52.1 years STANDARD_DEVIATION 14.92 | 52.6 years STANDARD_DEVIATION 14.76 |
| Age, Customized Randomized Age Group Strata, Categorical <=70 years | 472 Participants | 945 Participants | 473 Participants |
| Age, Customized Randomized Age Group Strata, Categorical >70 years | 56 Participants | 112 Participants | 56 Participants |
| Age, Customized | 53 years | 53 years | 53 years |
| BMI | 32.3 kg/m^2 STANDARD_DEVIATION 6.7 | 32.3 kg/m^2 STANDARD_DEVIATION 6.6 | 32.2 kg/m^2 STANDARD_DEVIATION 6.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 345 Participants | 691 Participants | 346 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 183 Participants | 366 Participants | 183 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 24 Participants | 45 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 40 Participants | 82 Participants | 42 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 458 Participants | 921 Participants | 463 Participants |
| Region of Enrollment Brazil | 11 participants | 22 participants | 11 participants |
| Region of Enrollment Canada | 24 participants | 52 participants | 28 participants |
| Region of Enrollment Peru | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Spain | 14 participants | 29 participants | 15 participants |
| Region of Enrollment United States | 479 participants | 953 participants | 474 participants |
| Sex: Female, Male Female | 299 Participants | 572 Participants | 273 Participants |
| Sex: Female, Male Male | 229 Participants | 485 Participants | 256 Participants |
| Weight | 89.5 kg STANDARD_DEVIATION 21.5 | 89.8 kg STANDARD_DEVIATION 21.4 | 90.05 kg STANDARD_DEVIATION 21.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 523 | 5 / 526 |
| other Total, other adverse events | 26 / 523 | 31 / 526 |
| serious Total, serious adverse events | 11 / 523 | 35 / 526 |
Outcome results
Primary
Number of Participants Who Had Progression of COVID-19 Through Day 29
COVID-19 progression defined as hospitalization \>24 hours or death
Time frame: Through Day 29
Population: Intent-to-Treat (All participants who were randomly assigned to study intervention)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | Number of Participants Who Had Progression of COVID-19 Through Day 29 | 6 Participants |
| Placebo | Number of Participants Who Had Progression of COVID-19 Through Day 29 | 30 Participants |
p-value: <0.00195% CI: [0.09, 0.5]poisson regression model
Secondary
29-day All-cause Mortality
Participants alive at the respective follow-up timepoint were censored at that timepoint; participants who withdrew prior to the respective timepoint were censored at the time of study withdrawal
Time frame: Through Day 29
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | 29-day All-cause Mortality | 0 Participants |
| Placebo | 29-day All-cause Mortality | 2 Participants |
Secondary
60-day All-cause Mortality
Participants alive at the respective follow-up timepoint were censored at that timepoint; participants who withdrew prior to the respective timepoint were censored at the time of study withdrawal
Time frame: Through Day 60
Population: Intent-to-Treat (All participants who were randomly assigned to study intervention)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | 60-day All-cause Mortality | 0 Participants |
| Placebo | 60-day All-cause Mortality | 4 Participants |
Secondary
90-day All-cause Mortality
Participants alive at the respective follow-up timepoint were censored at that timepoint; participants who withdrew prior to the respective timepoint were censored at the time of study withdrawal
Time frame: Through Day 90
Population: Intent-to-Treat (All participants who were randomly assigned to study intervention)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | 90-day All-cause Mortality | 0 Participants |
| Placebo | 90-day All-cause Mortality | 4 Participants |
Secondary
Apparent Volume of Distribution at Steady State (Vss) of VIR-7831 Following IV Administration
Time frame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Population: Participants in the Lead-in phase (n=10) who received 500 mg sotrovimab administered intravenously (IV). One subject was excluded from summary due to insufficient data (no data past study Day 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sotrovimab (500 mg IV) | Apparent Volume of Distribution at Steady State (Vss) of VIR-7831 Following IV Administration | 6.93 Liter | Geometric Coefficient of Variation 11.59 |
Secondary
Apparent Volume of Distribution During the Elimination Phase (Vz) of VIR-7831 Following IV Administration
Time frame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Population: Participants in the Lead-in phase (n=10) who received 500 mg sotrovimab administered intravenously (IV). One subject was excluded from summary due to insufficient data (no data past study Day 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sotrovimab (500 mg IV) | Apparent Volume of Distribution During the Elimination Phase (Vz) of VIR-7831 Following IV Administration | 7.52 Liter | Geometric Coefficient of Variation 13.77 |
Secondary
Area Under the Serum Concentration-time Curve Extrapolated From Zero to Infinity (AUCinf) of VIR-7831 After IV Administration
Time frame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Population: Participants in the Lead-in phase (n=10) who received 500 mg sotrovimab administered intravenously (IV). One subject was excluded from summary due to insufficient data (no data past study Day 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sotrovimab (500 mg IV) | Area Under the Serum Concentration-time Curve Extrapolated From Zero to Infinity (AUCinf) of VIR-7831 After IV Administration | 5536.9 day*μg/mL | Geometric Coefficient of Variation 25.18 |
Secondary
Area Under the Serum Concentration-time Curve From the Time of Dosing to the Time of the Last Measurable (Positive) Concentration (AUClast) of VIR-7831 After IV Administration
Time frame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Population: Participants in the Lead-in phase (n=10) who received 500 mg sotrovimab administered intravenously (IV). One subject was excluded from summary due to insufficient data (no data past study Day 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sotrovimab (500 mg IV) | Area Under the Serum Concentration-time Curve From the Time of Dosing to the Time of the Last Measurable (Positive) Concentration (AUClast) of VIR-7831 After IV Administration | 4777.7 day*μg/mL | Geometric Coefficient of Variation 20.15 |
Secondary
Change From Baseline in Viral Load in Nasal Secretions by qRT-PCR at Day 8
Time frame: Baseline and Day 8
Population: Participants in the Virology analysis population (all participants who were randomly assigned to study intervention with a central lab confirmed quantifiable baseline nasopharyngeal swab) with analyzable data at Day 8
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sotrovimab (500 mg IV) | Change From Baseline in Viral Load in Nasal Secretions by qRT-PCR at Day 8 | -2.589 Log 10 copies/mL | Standard Error 0.0606 |
| Placebo | Change From Baseline in Viral Load in Nasal Secretions by qRT-PCR at Day 8 | -2.357 Log 10 copies/mL | Standard Error 0.0598 |
p-value: 0.00795% CI: [-0.399, -0.065]Mixed model repeated measures
Secondary
Clearance (CL) of VIR-7831 After IV Administration
Time frame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Population: Participants in the Lead-in phase (n=10) who received 500 mg sotrovimab administered intravenously (IV). One subject was excluded from summary due to insufficient data (no data past study Day 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sotrovimab (500 mg IV) | Clearance (CL) of VIR-7831 After IV Administration | 90.3 mL/day | Geometric Coefficient of Variation 25.18 |
Secondary
Concentration at the Last Quantifiable Time Point (Clast) of VIR-7831 After IV Administration
Time frame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Population: Participants in the Lead-in phase (n=10) who received 500 mg sotrovimab administered intravenously (IV). One subject was excluded from summary due to insufficient data (no data past study Day 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sotrovimab (500 mg IV) | Concentration at the Last Quantifiable Time Point (Clast) of VIR-7831 After IV Administration | 8.4 μg/mL | Geometric Coefficient of Variation 44.41 |
Secondary
Maximum Observed Concentration (Cmax) of VIR-7831 After IV Administration
Time frame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Population: Participants in the Lead-in phase (n=10) who received 500 mg sotrovimab administered intravenously (IV). One subject was excluded from summary due to insufficient data (no data before study Day 5).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sotrovimab (500 mg IV) | Maximum Observed Concentration (Cmax) of VIR-7831 After IV Administration | 245.6 μg/mL | Geometric Coefficient of Variation 39.44 |
Secondary
Mean Change in FLU PRO Plus Total Score (AUC)
Mean change in InFLUenza Patient-Reported Outcome (FLU-PRO Plus) questionnaire total score. The FLU-PRO is a 32-item daily diary assessing influenza symptoms and severity across 6 body systems (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic). The FLU-PRO Plus includes the 32-item FLU-PRO with 2 additional items for loss of smell and taste. The mean total score can range from 0 (symptom free) to 4 (very severe symptoms) and was calculated as the arithmetic mean of the 32 items within FLU-PRO. Missing total score at day 7 was imputed using a modified last observation carried forward approach.
Time frame: Through Day 7
Population: Intent-to-Treat (All participants who were randomly assigned to study intervention) with available FLU-PRO Plus total scores to calculate AUC through Day 7.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sotrovimab (500 mg IV) | Mean Change in FLU PRO Plus Total Score (AUC) | -3.05 Total symptom score x days |
| Placebo | Mean Change in FLU PRO Plus Total Score (AUC) | -1.98 Total symptom score x days |
p-value: <0.00195% CI: [-1.38, -0.76]ANCOVA
Secondary
Number of Participants Who Had Progression of COVID-19
COVID-19 progression defined as a visit to a hospital emergency room for management of illness or hospitalization for acute management of illness or death
Time frame: Through Day 29
Population: Intent-to-Treat (All participants who were randomly assigned to study intervention)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | Number of Participants Who Had Progression of COVID-19 | 13 Participants |
| Placebo | Number of Participants Who Had Progression of COVID-19 | 39 Participants |
p-value: <0.00195% CI: [0.19, 0.63]poisson regression model
Secondary
Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 15
Participants were defined as progression to severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progression to critical respiratory COVID-19 if they required invasive mechanical ventilation or ECMO.
Time frame: Through Day 15
Population: Intent-to-Treat (All participants who were randomly assigned to study intervention)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 15 | 6 Participants |
| Placebo | Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 15 | 28 Participants |
Secondary
Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 22
Participants were defined as progression to severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progression to critical respiratory COVID-19 if they required invasive mechanical ventilation or ECMO.
Time frame: Through Day 22
Population: Intent-to-Treat (All participants who were randomly assigned to study intervention)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 22 | 7 Participants |
| Placebo | Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 22 | 28 Participants |
Secondary
Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 29
Participants were defined as progression to severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progression to critical respiratory COVID-19 if they required invasive mechanical ventilation or ECMO.
Time frame: Through Day 29
Population: Intent-to-Treat (All participants who were randomly assigned to study intervention)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 29 | 7 Participants |
| Placebo | Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 29 | 28 Participants |
p-value: 0.00295% CI: [0.12, 0.59]poisson regression model
Secondary
Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 8
Time frame: Through Day 8
Population: Intent-to-Treat (All participants who were randomly assigned to study intervention)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 8 | 6 Participants |
| Placebo | Number of Participants Who Progressed to Develop Severe and/or Critical Respiratory COVID-19 as Manifested by Requirement for and Method of Supplemental Oxygen Through Day 8 | 20 Participants |
Secondary
Number of Participants With Adverse Events (AEs)
Time frame: Up to 24 weeks
Population: All participants who received at least one dose of study intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | Number of Participants With Adverse Events (AEs) | 133 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | 140 Participants |
Secondary
Number of Participants With Cardiac Events of Special Interest
Time frame: Up to 24 weeks
Population: All participants who received at least one dose of study intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | Number of Participants With Cardiac Events of Special Interest | 1 Participants |
| Placebo | Number of Participants With Cardiac Events of Special Interest | 0 Participants |
Secondary
Number of Participants With Infusion-related Reactions (IRR) Including Hypersensitivity Reactions
Time frame: Up to 24 weeks
Population: All participants who received at least one dose of study intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | Number of Participants With Infusion-related Reactions (IRR) Including Hypersensitivity Reactions | 7 Participants |
| Placebo | Number of Participants With Infusion-related Reactions (IRR) Including Hypersensitivity Reactions | 6 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs)
Time frame: Up to 24 weeks
Population: All participants who received at least one dose of study intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | Number of Participants With Serious Adverse Events (SAEs) | 11 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) | 35 Participants |
Secondary
Number of Participants With Serum Anti-drug Antibody (ADA) to Sotrovimab
Time frame: Up to 24 weeks
Population: Number of subjects with any post-baseline ADA result
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotrovimab (500 mg IV) | Number of Participants With Serum Anti-drug Antibody (ADA) to Sotrovimab | 65 Participants |
| Placebo | Number of Participants With Serum Anti-drug Antibody (ADA) to Sotrovimab | 0 Participants |
Secondary
Percentage of AUCinf Obtained by Extrapolation (%AUCexp) for VIR-7831 After IV Administration
Time frame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Population: Participants in the Lead-in phase (n=10) who received 500 mg sotrovimab administered intravenously (IV). One subject was excluded from summary due to insufficient data (no data past study Day 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Sotrovimab (500 mg IV) | Percentage of AUCinf Obtained by Extrapolation (%AUCexp) for VIR-7831 After IV Administration | 12.6 percentage | Geometric Coefficient of Variation 41.26 |
Secondary
Terminal Elimination Half-life (t1/2) of VIR-7831 After IV Administration
Time frame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Population: Participants in the Lead-in phase (n=10) who received 500 mg sotrovimab administered intravenously (IV). One subject was excluded from summary due to insufficient data (no data past study Day 2).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sotrovimab (500 mg IV) | Terminal Elimination Half-life (t1/2) of VIR-7831 After IV Administration | 56.5 day |
Secondary
Time of the Last Quantifiable Concentration (Tlast) of VIR-7831 After IV Administration
Time frame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Population: Participants in the Lead-in phase (n=10) who received 500 mg sotrovimab administered intravenously (IV). One subject was excluded from summary due to insufficient data (no data past study Day 2).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sotrovimab (500 mg IV) | Time of the Last Quantifiable Concentration (Tlast) of VIR-7831 After IV Administration | 161 day |
Secondary
Time to Reach the Maximum Concentration (Tmax) of VIR-7831 After IV Administration
Time frame: Day 1: Pre-dose, and end of infusion; Days 2, 5, 8, 15, 29, 43, 57, 85, 141, 169
Population: Participants in the Lead-in phase (n=10) who received 500 mg sotrovimab administered intravenously (IV). One subject was excluded from summary due to insufficient data (no data before study Day 5).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sotrovimab (500 mg IV) | Time to Reach the Maximum Concentration (Tmax) of VIR-7831 After IV Administration | 0.04 day |
Secondary
Time to Symptom Alleviation Using FLU-PRO Plus
Symptom alleviation is defined as absence of the majority of core symptoms of COVID-19 (except for cough or fatigue, where scoring no more than 'somewhat' in severity, and loss of smell or taste were allowed) as measured by FLU-PRO Plus, sustained for \>=48 hours. Participants could only achieve sustained symptom alleviation following \>=2 non-missing consecutively scored questionnaires that showed symptom alleviation. Participants who did not achieve sustained symptom alleviation were censored at Day 21, the day of death, or the day of withdrawal, whichever was earliest. Days where symptom alleviation could not be assessed to a missing/incomplete questionnaire were imputed as no symptom alleviation. The FLU-PRO is a 32-item daily diary assessing influenza symptoms and severity across 6 body systems (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic). The FLU-PRO Plus includes the 32-item FLU-PRO with 2 additional items for loss of smell and taste.
Time frame: Through Day 21
Population: Intent-to-Treat (All participants who were randomly assigned to study intervention)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sotrovimab (500 mg IV) | Time to Symptom Alleviation Using FLU-PRO Plus | NA Days |
| Placebo | Time to Symptom Alleviation Using FLU-PRO Plus | NA Days |
Secondary
Titers of Serum Anti-drug Antibody (ADA) to Sotrovimab
Titers defined as the reciprocal of the highest dilution of the sample (including minimum required dilution) that yields a positive result.
Time frame: Up to 24 Weeks
Population: Safety (subjects with any post-baseline ADA)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sotrovimab (500 mg IV) | Titers of Serum Anti-drug Antibody (ADA) to Sotrovimab | Treatment-unaffected | 10 Titer |
| Sotrovimab (500 mg IV) | Titers of Serum Anti-drug Antibody (ADA) to Sotrovimab | Treatment-induced | 40 Titer |
| Sotrovimab (500 mg IV) | Titers of Serum Anti-drug Antibody (ADA) to Sotrovimab | Treatment-boosted | 80 Titer |
| Placebo | Titers of Serum Anti-drug Antibody (ADA) to Sotrovimab | Treatment-unaffected | 0 Titer |
| Placebo | Titers of Serum Anti-drug Antibody (ADA) to Sotrovimab | Treatment-induced | 0 Titer |
| Placebo | Titers of Serum Anti-drug Antibody (ADA) to Sotrovimab | Treatment-boosted | 0 Titer |