Covid19
Conditions
Keywords
SARS-CoV-2, coronavirus disease 2019, COVID-19, early treatment, coronavirus
Brief summary
The COMET-TAIL main study evaluated efficacy, safety, and tolerability of IM sotrovimab versus IV sotrovimab in high-risk patients for the treatment of mild/moderate COVID-19. In the safety substudy, the aim was to evaluate the safety and tolerability of sotrovimab across a single ascending dose level and over different infusion times when given for the treatment of mild/moderate COVID-19 to participants at high risk of disease progression Main study was completed successfully. The safety sub-study was discontinued early in the context of evolving variants with increased fold changes in the in vitro half maximal inhibitory concentration (IC50) and uncertainty in the clinical relevance of these changes.
Interventions
BIOLOGICALsotrovimab
Sotrovimab 500 mg given by intravenous infusion over 15 min
BIOLOGICALSotrovimab
Sotrovimab 2000 mg given by intravenous infusion over 30 min
Sponsors
GlaxoSmithKline
Vir Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Main Study participant must be aged 12 years or older AND at high risk of progression of COVID-19 or \> 55 years old * Sub-Study participants must be aged 18 years or older at time of consent 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 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 * Known hypersensitivity to any constituent present in the investigational product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Main Study: Percentage of Participants Who Had Progression of Coronavirus Disease 2019 (COVID-19) Through Day 29 by Hospitalization >24 Hours or Death Due to Any Cause (Weekly and Daily Imputation) | Up to Day 29 | Progression of COVID-19 through Day 29 as defined by hospitalization \>24 hours for acute management of illness due to any cause or death. Percentage values are rounded off. |
| Safety Sub-study: Number of Participants With Non-Serious Adverse Events (Non-SAE) and Serious Adverse Events (SAEs) Through Day 8 | Up to Day 8 | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other situation according to medical or scientific judgement. Adverse events which were not Serious were considered as Non-Serious adverse events. |
| Safety Sub-study: Number of Participants With Infusion-related Reaction Including Hypersensitivity Through Day 8 | Up to Day 8 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Adverse events of special interest (AESI) included infusion-related reaction including hypersensitivity. Data for number of participants with infusion-related reaction including hypersensitivity has been presented. |
| Safety Sub-study: Number of Participants With Any Disease Related Events Through Day 8 | Up to Day 8 | AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Main Study: Number of Participants With Any Disease Related Events | Up to 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, were reported as a disease related events. |
| Safety Sub-study: Number of Participants With Non-SAEs Through Week 12 | Up to 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 no serious, were considered as non-SAEs. |
| Safety Sub-study: Number of Participants With SAEs Through Week 36 | Up to Week 36 | An SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other situation according to medical or scientific judgement. |
| Safety Sub-study: Number of Participants With Any Infusion-related Reaction Including Hypersensitivity Through Week 12 | Up to 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. AESI is infusion-related reaction including hypersensitivity. |
| Safety Sub-study: Number of Participants With Any Disease Related Events Through Week 12 | Up to Week 12 | AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events. |
| Main Study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody | Up to Week 24 | Serum samples were collected for the determination of anti-drug antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. |
| Main Study: Titers of Anti-drug Antibodies Against Sotrovimab | Up to Week 24 | Confirmed positive ADA samples were further analyzed to obtain the titer of the antibodies. Titer is defined as the reciprocal of the highest dilution that yield results at or above the plate-based titer cut point x MRD. Titer Median and range from treatment emergent and unaffected are described below. Immunogenicity results were categorized as treatment- induced, treatment-boosted, and treatment-unaffected. Treatment-induced=those who are ADA negative or missing data at baseline and who have at least one post-dose ADA positive sample; Treatment boosted=those who are ADA positive at baseline and have a \>4\*Baseline titer; Treatment unaffected=those who are positive at baseline and post-Baseline titer \<=4\*Baseline titer or all post- Baseline negative. Treatment emergent = treatment induced or treatment boosted |
| Safety Sub-study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody Through Week 24 | Up to Week 24 | Serum samples were collected for the determination of anti-drug antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. |
| Safety Sub-study: Titers of Anti-drug Antibodies Against Sotrovimab Through Week 24 | Up to Week 24 | Confirmed positive ADA samples were further analyzed to obtain the titer of the antibodies. Titer is defined as the reciprocal of the highest dilution that yield results at or above the plate-based titer cut point x MRD. Titer Median and range from treatment emergent and unaffected are described below. Immunogenicity results were categorized as treatment- induced, treatment-boosted, and treatment-unaffected. Treatment-induced=those who are ADA negative or missing data at baseline and who have at least one post-dose ADA positive sample; Treatment boosted=those who are ADA positive at baseline and have a \>4\*Baseline titer; Treatment unaffected=those who are positive at baseline and post-Baseline titer \<=4\*Baseline titer or all post- Baseline negative. Treatment emergent = treatment induced or treatment boosted |
| Safety Sub-study: Number of Participants With Positive Neutralizing Antibodies | Up to Week 24 | Blood samples were collected for the determination of positive neutralizing antibodies. A neutralizing antibody assay was performed. Neutralizing antibody test was only carried out for participants who have had a positive confirmatory binding antibody test result at visit. A participant was considered positive if they had at least one positive post-Baseline neutralizing antibody result. |
| Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. |
| Main Study: Percentage of Participants Who Had Progression of COVID-19 Through Day 29 by Emergency Room Visit or Hospitalization or Death (Weekly Imputation) | Up to Day 29 | Progression of COVID-19 through Day 29 as defined by visit to a hospital emergency room for management of illness or hospitalization for acute management of illness for any duration and for any cause or death. Percentage values are rounded off. |
| Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 8, Day 15, Day 22, and Day 29 | Participants were defined as progressing to develop severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progressing to develop critical respiratory COVID-19 if they required invasive mechanical ventilation or extracorporeal membrane oxygenation. Percentage values are rounded off. |
| Main Study: Number of Participants With Common Non-Serious Adverse Events (Non-SAEs) | Up to 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. Data for Common (\>=1%) non-SAEs are presented. |
| Main Study: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 After Administration of Sotrovimab 500 mg IV and IM | Day 1 to Day 8 | AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 8 in nasopharyngeal swab samples. Least squares geometric mean and 90 percent (%) confidence interval has been presented. |
| Main Study: Change From Baseline in Viral Load as Measured by qRT-PCR at Day 8 | Baseline (Day 1) and at Day 8 | Viral load was based on nasopharyngeal swab samples and was measured by qRT-PCR. Baseline was defined as the latest non-missing value prior to dosing (or latest value on or prior to nominal Day 1 for participants that were not dosed). Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. |
| Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8 | 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 SARS-CoV-2 viral load at Day 8 was assessed via qRT-PCR in nasopharyngeal swab samples. Percentage values are rounded off. |
| Main Study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. |
| Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24 | Blood samples were collected at indicated time points for PK analysis of Sotrovimab. |
| Safety Sub-study: Area Under the Serum Concentration-time Curve From Days 1 to 29 of After Intravenous Administration (AUCD1-29) of Sotrovimab | Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method. |
| Safety Sub-study: Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Cmax) | Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method. |
| Safety Sub-study: Apparent Volume of Distribution at Steady State of Sotrovimab After Intravenous Administration (Vss) | Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method. |
| Safety Sub-study: Area Under the Serum Concentration-Time Curve Extrapolated From Zero to Infinity of Sotrovimab After Intravenous Administration (AUC[0-inf]) | Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method. |
| Safety Sub-study: Terminal Elimination Half-life of Sotrovimab After Intravenous Administration (t1/2) | Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method. |
| Safety Sub-study: Apparent Volume of Distribution During the Elimination Phase of Sotrovimab After Intravenous Administration (Vz) | Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method. |
| Safety Sub-study: Clearance of Sotrovimab After Intravenous Administration (CL) | Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method. |
| Safety Sub-study: Time to Reach Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Tmax) | Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method. |
| Main Study: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8 | Day 1 to Day 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 swab samples. |
| Main Study: Number of Participants With Serious Adverse Events (SAEs) | Up to Week 36 | An SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before. |
| Main Study: Number of Participants With Any Infusion- or Injection-related Reaction Including Hypersensitivity | Up to Week 36 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESI included infusion- or injection-related reaction including hypersensitivity. Data for number of participants with any infusion- or injection-related reaction including hypersensitivity has been presented. |
| Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration | Up to Week 36 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs included any solicited local site reactions. AESI were graded according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 2007, Food and Drug Administration, where Grade 1=Mild toxicity; Grade 2=Moderate toxicity; Grade 3=Severe toxicity; and Grade 4= Potentially life-threatening toxicity. Higher Grade indicates higher severity. Data for any worst case post-Baseline has been presented. |
Countries
France, Ukraine, United States
Participant flow
Recruitment details
This study consists of Main study and Safety sub-study. Main study was completed successfully. The safety sub-study was discontinued early in the context of evolving variants with increased fold changes in the in vitro half maximal inhibitory concentration (IC50) and uncertainty in the clinical relevance of these changes.
Pre-assignment details
A total of 1065 participants were enrolled in this study (983 in main study and 82 in safety sub-study), of which 10 participants from main study and 1 from safety sub-study did not receive study intervention. Hence, a total of 973 from main study and 81 from safety sub-study were exposed to study intervention constituting the Safety Populations.
Participants by arm
| Arm | Count |
|---|---|
| Main Study: Sotrovimab 500 mg IV Participants received a single dose of sotrovimab 500 milligram (mg), IV infusion over 15 minutes on Day 1. | 393 |
| Main Study: Sotrovimab 500 mg IM Participants received a single dose of sotrovimab 500 mg, IM dose as 2\*4 milliliter (mL) injections in each dorsogluteal muscle on Day 1. | 385 |
| Main Study: Sotrovimab 250 mg IM Participants received a single dose of sotrovimab 250 mg, IM dose either as a single 250 mg (4 mL) injection in the dorsogluteal muscle or as 2\*2 mL injections in each deltoid muscle on Day 1. | 195 |
| Safety Sub-study: Sotrovimab (2000 mg IV) Participants received a single dose of sotrovimab 2000 mg, IV infusion over 60 minutes. | 81 |
| Total | 1,054 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Main Study (Up to Week 36) | Death | 0 | 2 | 2 | 0 |
| Main Study (Up to Week 36) | Lost to Follow-up | 12 | 8 | 4 | 0 |
| Main Study (Up to Week 36) | Physician Decision | 0 | 1 | 1 | 0 |
| Main Study (Up to Week 36) | Withdrawal by Subject | 25 | 33 | 12 | 0 |
| Safety Sub-study (Up to Week 36) | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Main Study: Sotrovimab 500 mg IV | Main Study: Sotrovimab 500 mg IM | Main Study: Sotrovimab 250 mg IM | Safety Sub-study: Sotrovimab (2000 mg IV) | Total |
|---|---|---|---|---|---|
| Age, Customized 12-17 years | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Age, Customized 18-64 years | 291 Participants | 289 Participants | 163 Participants | 66 Participants | 809 Participants |
| Age, Customized >=65 years | 100 Participants | 96 Participants | 31 Participants | 15 Participants | 242 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 17 Participants | 19 Participants | 8 Participants | 4 Participants | 48 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Mixed Race | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 10 Participants | 21 Participants | 8 Participants | 0 Participants | 39 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European | 362 Participants | 336 Participants | 176 Participants | 77 Participants | 951 Participants |
| Sex: Female, Male Female | 224 Participants | 197 Participants | 113 Participants | 47 Participants | 581 Participants |
| Sex: Female, Male Male | 169 Participants | 188 Participants | 82 Participants | 34 Participants | 473 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 393 | 2 / 385 | 2 / 195 | 0 / 81 |
| other Total, other adverse events | 8 / 393 | 5 / 385 | 12 / 195 | 0 / 81 |
| serious Total, serious adverse events | 3 / 393 | 7 / 385 | 3 / 195 | 1 / 81 |
Outcome results
Primary
Main Study: Percentage of Participants Who Had Progression of Coronavirus Disease 2019 (COVID-19) Through Day 29 by Hospitalization >24 Hours or Death Due to Any Cause (Weekly and Daily Imputation)
Progression of COVID-19 through Day 29 as defined by hospitalization \>24 hours for acute management of illness due to any cause or death. Percentage values are rounded off.
Time frame: Up to Day 29
Population: Primary Analysis Population consisted of all randomized participants excluding participants who were randomized under Protocol Amendment Version 1 and were immunocompetent and fully vaccinated at randomization and participants who did not meet key eligibility criteria. The statistical analysis was performed only for 500 mg IV versus 500 mg IM dose. It was not planned for 250 mg IM dose per statistical analysis plan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Percentage of Participants Who Had Progression of Coronavirus Disease 2019 (COVID-19) Through Day 29 by Hospitalization >24 Hours or Death Due to Any Cause (Weekly and Daily Imputation) | 1.3 Percentage of participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Percentage of Participants Who Had Progression of Coronavirus Disease 2019 (COVID-19) Through Day 29 by Hospitalization >24 Hours or Death Due to Any Cause (Weekly and Daily Imputation) | 2.7 Percentage of participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Percentage of Participants Who Had Progression of Coronavirus Disease 2019 (COVID-19) Through Day 29 by Hospitalization >24 Hours or Death Due to Any Cause (Weekly and Daily Imputation) | 5.5 Percentage of participants |
95% CI: [-1.15, 3.26]
95% CI: [-1.23, 3.56]
Primary
Safety Sub-study: Number of Participants With Any Disease Related Events Through Day 8
AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events.
Time frame: Up to Day 8
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Number of Participants With Any Disease Related Events Through Day 8 | 2 Participants |
Primary
Safety Sub-study: Number of Participants With Infusion-related Reaction Including Hypersensitivity Through Day 8
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Adverse events of special interest (AESI) included infusion-related reaction including hypersensitivity. Data for number of participants with infusion-related reaction including hypersensitivity has been presented.
Time frame: Up to Day 8
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Number of Participants With Infusion-related Reaction Including Hypersensitivity Through Day 8 | 0 Participants |
Primary
Safety Sub-study: Number of Participants With Non-Serious Adverse Events (Non-SAE) and Serious Adverse Events (SAEs) Through Day 8
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose: results in death; is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other situation according to medical or scientific judgement. Adverse events which were not Serious were considered as Non-Serious adverse events.
Time frame: Up to Day 8
Population: Safety Population consisted of all enrolled participants who were exposed to study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Number of Participants With Non-Serious Adverse Events (Non-SAE) and Serious Adverse Events (SAEs) Through Day 8 | Non-SAE | 0 Participants |
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Number of Participants With Non-Serious Adverse Events (Non-SAE) and Serious Adverse Events (SAEs) Through Day 8 | SAE | 0 Participants |
Secondary
Main Study: Change From Baseline in Viral Load as Measured by qRT-PCR at Day 8
Viral load was based on nasopharyngeal swab samples and was measured by qRT-PCR. Baseline was defined as the latest non-missing value prior to dosing (or latest value on or prior to nominal Day 1 for participants that were not dosed). Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1) and at Day 8
Population: Virology Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Change From Baseline in Viral Load as Measured by qRT-PCR at Day 8 | -2.979 Log10 copies/mL | Standard Deviation 1.6965 |
| Main Study: Sotrovimab 500 mg IM | Main Study: Change From Baseline in Viral Load as Measured by qRT-PCR at Day 8 | -2.752 Log10 copies/mL | Standard Deviation 1.7594 |
| Main Study: Sotrovimab 250 mg IM | Main Study: Change From Baseline in Viral Load as Measured by qRT-PCR at Day 8 | -2.488 Log10 copies/mL | Standard Deviation 1.6628 |
Secondary
Main Study: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8
AUC of SARS-CoV-2 viral load was measured by Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) from Day 1 to Day 8 in nasopharyngeal swab samples.
Time frame: Day 1 to Day 8
Population: Virology Population consisted of all participants in the ITT Population with a central laboratory confirmed quantifiable Baseline nasopharyngeal swab at Day 1. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8 | 25.42 Day*log10 copies/mL | Geometric Coefficient of Variation 34.144 |
| Main Study: Sotrovimab 500 mg IM | Main Study: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8 | 25.56 Day*log10 copies/mL | Geometric Coefficient of Variation 36.936 |
| Main Study: Sotrovimab 250 mg IM | Main Study: Mean Area Under the Curve (AUC) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Viral Load From Day 1 to Day 8 | 25.46 Day*log10 copies/mL | Geometric Coefficient of Variation 37.899 |
Secondary
Main Study: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 After Administration of Sotrovimab 500 mg IV and IM
AUC of SARS-CoV-2 viral load was measured by qRT-PCR from Day 1 to Day 8 in nasopharyngeal swab samples. Least squares geometric mean and 90 percent (%) confidence interval has been presented.
Time frame: Day 1 to Day 8
Population: Virology Population. Only those participants with data available at the specified time points were analyzed. The statistical analysis was performed only for 500 mg IV versus 500 mg IM dose. It was not planned for 250 mg IM dose per statistical analysis plan.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 After Administration of Sotrovimab 500 mg IV and IM | 25.03 Day*log10 copies/mL |
| Main Study: Sotrovimab 500 mg IM | Main Study: Mean AUC of SARS-CoV-2 Viral Load From Day 1 to Day 8 After Administration of Sotrovimab 500 mg IV and IM | 25.96 Day*log10 copies/mL |
90% CI: [1, 1.07]
Secondary
Main Study: Number of Participants With Any Disease Related Events
AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events.
Time frame: Up to Week 36
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Number of Participants With Any Disease Related Events | 18 Participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Number of Participants With Any Disease Related Events | 16 Participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Number of Participants With Any Disease Related Events | 20 Participants |
Secondary
Main Study: Number of Participants With Any Infusion- or Injection-related Reaction Including Hypersensitivity
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESI included infusion- or injection-related reaction including hypersensitivity. Data for number of participants with any infusion- or injection-related reaction including hypersensitivity has been presented.
Time frame: Up to Week 36
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Number of Participants With Any Infusion- or Injection-related Reaction Including Hypersensitivity | 2 Participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Number of Participants With Any Infusion- or Injection-related Reaction Including Hypersensitivity | 1 Participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Number of Participants With Any Infusion- or Injection-related Reaction Including Hypersensitivity | 1 Participants |
Secondary
Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs included any solicited local site reactions. AESI were graded according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 2007, Food and Drug Administration, where Grade 1=Mild toxicity; Grade 2=Moderate toxicity; Grade 3=Severe toxicity; and Grade 4= Potentially life-threatening toxicity. Higher Grade indicates higher severity. Data for any worst case post-Baseline has been presented.
Time frame: Up to Week 36
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration | Grade 1 | 39 Participants |
| Main Study: Sotrovimab 500 mg IV | Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration | Grade 2 | 7 Participants |
| Main Study: Sotrovimab 500 mg IV | Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration | Grade 3 | 1 Participants |
| Main Study: Sotrovimab 500 mg IV | Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration | Grade 4 | 0 Participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration | Grade 4 | 0 Participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration | Grade 1 | 22 Participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration | Grade 3 | 0 Participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Number of Participants With Any Local Site Reaction by Maximum Severity After IM Administration | Grade 2 | 2 Participants |
Secondary
Main Study: Number of Participants With Common Non-Serious Adverse Events (Non-SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Data for Common (\>=1%) non-SAEs are presented.
Time frame: Up to Week 12
Population: Safety Population consisted of all randomized participants who were exposed to study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Number of Participants With Common Non-Serious Adverse Events (Non-SAEs) | 8 Participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Number of Participants With Common Non-Serious Adverse Events (Non-SAEs) | 5 Participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Number of Participants With Common Non-Serious Adverse Events (Non-SAEs) | 12 Participants |
Secondary
Main Study: Number of Participants With Serious Adverse Events (SAEs)
An SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, significant medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed before.
Time frame: Up to Week 36
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Number of Participants With Serious Adverse Events (SAEs) | 3 Participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Number of Participants With Serious Adverse Events (SAEs) | 7 Participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Number of Participants With Serious Adverse Events (SAEs) | 3 Participants |
Secondary
Main Study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody
Serum samples were collected for the determination of anti-drug antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample.
Time frame: Up to Week 24
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody | 25 Participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody | 51 Participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody | 26 Participants |
Secondary
Main Study: Percentage of Participants Who Had Progression of COVID-19 Through Day 29 by Emergency Room Visit or Hospitalization or Death (Weekly Imputation)
Progression of COVID-19 through Day 29 as defined by visit to a hospital emergency room for management of illness or hospitalization for acute management of illness for any duration and for any cause or death. Percentage values are rounded off.
Time frame: Up to Day 29
Population: Primary Analysis Population. The statistical analysis was performed only for 500 mg IV versus 500 mg IM dose. It was not planned for 250 mg IM dose per statistical analysis plan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Percentage of Participants Who Had Progression of COVID-19 Through Day 29 by Emergency Room Visit or Hospitalization or Death (Weekly Imputation) | 2.4 Percentage of participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Percentage of Participants Who Had Progression of COVID-19 Through Day 29 by Emergency Room Visit or Hospitalization or Death (Weekly Imputation) | 3.2 Percentage of participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Percentage of Participants Who Had Progression of COVID-19 Through Day 29 by Emergency Room Visit or Hospitalization or Death (Weekly Imputation) | 6.0 Percentage of participants |
95% CI: [-1.56, 3.28]
Secondary
Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit
Participants were defined as progressing to develop severe respiratory COVID-19 if they required supplemental oxygen either by nasal cannula, face mask, high-flow oxygen devices, or non-invasive ventilation. Participants were defined as progressing to develop critical respiratory COVID-19 if they required invasive mechanical ventilation or extracorporeal membrane oxygenation. Percentage values are rounded off.
Time frame: Day 8, Day 15, Day 22, and Day 29
Population: Intent-to-Treat (ITT) Population consisted of all randomized participants excluding participants who were randomized under Protocol Amendment Version 1 and were immunocompetent and fully vaccinated at randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 8 | 0.3 Percentage of participants |
| Main Study: Sotrovimab 500 mg IV | Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 15 | 0.3 Percentage of participants |
| Main Study: Sotrovimab 500 mg IV | Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 22 | 0.3 Percentage of participants |
| Main Study: Sotrovimab 500 mg IV | Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 29 | 0.3 Percentage of participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 29 | 1.6 Percentage of participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 8 | 1.0 Percentage of participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 22 | 1.6 Percentage of participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 15 | 1.3 Percentage of participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 29 | 4.3 Percentage of participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 15 | 4.3 Percentage of participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 22 | 4.3 Percentage of participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Percentage of Participants Who Progress to Develop Severe and/or Critical Respiratory COVID-19 by Visit | Day 8 | 3.8 Percentage of participants |
Secondary
Main Study: Percentage of Participants With Persistently High SARS-CoV-2 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 SARS-CoV-2 viral load at Day 8 was assessed via qRT-PCR in nasopharyngeal swab samples. Percentage values are rounded off.
Time frame: At Day 8
Population: Virology Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8 | >=4.1 log 10 copies/mL | 13 Percentage of participants |
| Main Study: Sotrovimab 500 mg IV | Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8 | <4.1 log 10 copies/mL | 87 Percentage of participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8 | >=4.1 log 10 copies/mL | 12 Percentage of participants |
| Main Study: Sotrovimab 500 mg IM | Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8 | <4.1 log 10 copies/mL | 88 Percentage of participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8 | >=4.1 log 10 copies/mL | 17 Percentage of participants |
| Main Study: Sotrovimab 250 mg IM | Main Study: Percentage of Participants With Persistently High SARS-CoV-2 Viral Load at Day 8 | <4.1 log 10 copies/mL | 83 Percentage of participants |
Secondary
Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration
Blood samples were collected at indicated time points for PK analysis of Sotrovimab.
Time frame: Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24
Population: Pharmacokinetic Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Day 15 | 20.60 Microgram per mL | Geometric Coefficient of Variation 84.01 |
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Week 12 | 11.15 Microgram per mL | Geometric Coefficient of Variation 64.01 |
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Day 8 | 20.50 Microgram per mL | Geometric Coefficient of Variation 88.7 |
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Week 20 | 5.83 Microgram per mL | Geometric Coefficient of Variation 65.44 |
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Day 29 | 18.92 Microgram per mL | Geometric Coefficient of Variation 77 |
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Week 24 | 4.48 Microgram per mL | Geometric Coefficient of Variation 71.57 |
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Day 1: Pre-dose | NA Microgram per mL | — |
| Main Study: Sotrovimab 500 mg IM | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Week 24 | 2.34 Microgram per mL | Geometric Coefficient of Variation 62.49 |
| Main Study: Sotrovimab 500 mg IM | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Day 1: Pre-dose | NA Microgram per mL | — |
| Main Study: Sotrovimab 500 mg IM | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Day 8 | 10.93 Microgram per mL | Geometric Coefficient of Variation 92.47 |
| Main Study: Sotrovimab 500 mg IM | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Day 15 | 10.90 Microgram per mL | Geometric Coefficient of Variation 77.68 |
| Main Study: Sotrovimab 500 mg IM | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Day 29 | 10.20 Microgram per mL | Geometric Coefficient of Variation 61.8 |
| Main Study: Sotrovimab 500 mg IM | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Week 12 | 6.15 Microgram per mL | Geometric Coefficient of Variation 54.22 |
| Main Study: Sotrovimab 500 mg IM | Main Study: Serum Concentration of Sotrovimab After Intramuscular Administration | Week 20 | 3.19 Microgram per mL | Geometric Coefficient of Variation 57.05 |
Secondary
Main Study: Serum Concentration of Sotrovimab After Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab.
Time frame: Day 1: Pre-dose, Day 8, Day 15, Day 29, Week 12, Week 20 and Week 24
Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 1: Pre-dose | NA Microgram per mL | — |
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 8 | 53.67 Microgram per mL | Geometric Coefficient of Variation 54.21 |
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 15 | 44.62 Microgram per mL | Geometric Coefficient of Variation 51.54 |
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 29 | 33.89 Microgram per mL | Geometric Coefficient of Variation 72.61 |
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intravenous Administration | Week 12 | 19.10 Microgram per mL | Geometric Coefficient of Variation 55.2 |
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intravenous Administration | Week 20 | 9.96 Microgram per mL | Geometric Coefficient of Variation 53.24 |
| Main Study: Sotrovimab 500 mg IV | Main Study: Serum Concentration of Sotrovimab After Intravenous Administration | Week 24 | 7.66 Microgram per mL | Geometric Coefficient of Variation 56.73 |
Secondary
Main Study: Titers of Anti-drug Antibodies Against Sotrovimab
Confirmed positive ADA samples were further analyzed to obtain the titer of the antibodies. Titer is defined as the reciprocal of the highest dilution that yield results at or above the plate-based titer cut point x MRD. Titer Median and range from treatment emergent and unaffected are described below. Immunogenicity results were categorized as treatment- induced, treatment-boosted, and treatment-unaffected. Treatment-induced=those who are ADA negative or missing data at baseline and who have at least one post-dose ADA positive sample; Treatment boosted=those who are ADA positive at baseline and have a \>4\*Baseline titer; Treatment unaffected=those who are positive at baseline and post-Baseline titer \<=4\*Baseline titer or all post- Baseline negative. Treatment emergent = treatment induced or treatment boosted
Time frame: Up to Week 24
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Main Study: Titers of Anti-drug Antibodies Against Sotrovimab | Treatment-induced | 80.0 Titers |
| Main Study: Sotrovimab 500 mg IV | Main Study: Titers of Anti-drug Antibodies Against Sotrovimab | Treatment-unaffected | 40.0 Titers |
| Main Study: Sotrovimab 500 mg IM | Main Study: Titers of Anti-drug Antibodies Against Sotrovimab | Treatment-induced | 80.0 Titers |
| Main Study: Sotrovimab 500 mg IM | Main Study: Titers of Anti-drug Antibodies Against Sotrovimab | Treatment-unaffected | 60.0 Titers |
| Main Study: Sotrovimab 250 mg IM | Main Study: Titers of Anti-drug Antibodies Against Sotrovimab | Treatment-induced | 80.0 Titers |
| Main Study: Sotrovimab 250 mg IM | Main Study: Titers of Anti-drug Antibodies Against Sotrovimab | Treatment-unaffected | 40.0 Titers |
Secondary
Safety Sub-study: Apparent Volume of Distribution at Steady State of Sotrovimab After Intravenous Administration (Vss)
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Apparent Volume of Distribution at Steady State of Sotrovimab After Intravenous Administration (Vss) | 6.81 Liter | Geometric Coefficient of Variation 37.72 |
Secondary
Safety Sub-study: Apparent Volume of Distribution During the Elimination Phase of Sotrovimab After Intravenous Administration (Vz)
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Apparent Volume of Distribution During the Elimination Phase of Sotrovimab After Intravenous Administration (Vz) | 7.05 Liter | Geometric Coefficient of Variation 37.66 |
Secondary
Safety Sub-study: Area Under the Serum Concentration-Time Curve Extrapolated From Zero to Infinity of Sotrovimab After Intravenous Administration (AUC[0-inf])
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Area Under the Serum Concentration-Time Curve Extrapolated From Zero to Infinity of Sotrovimab After Intravenous Administration (AUC[0-inf]) | 23992.5 day*µg/mL | Geometric Coefficient of Variation 34.9 |
Secondary
Safety Sub-study: Area Under the Serum Concentration-time Curve From Days 1 to 29 of After Intravenous Administration (AUCD1-29) of Sotrovimab
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose
Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Area Under the Serum Concentration-time Curve From Days 1 to 29 of After Intravenous Administration (AUCD1-29) of Sotrovimab | 7493.9 day*µg/mL | Geometric Coefficient of Variation 34.68 |
Secondary
Safety Sub-study: Clearance of Sotrovimab After Intravenous Administration (CL)
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Clearance of Sotrovimab After Intravenous Administration (CL) | 83.4 mL/day | Geometric Coefficient of Variation 34.9 |
Secondary
Safety Sub-study: Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Cmax)
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Cmax) | 732.5 µg/mL | Geometric Coefficient of Variation 42.23 |
Secondary
Safety Sub-study: Number of Participants With Any Disease Related Events Through Week 12
AEs related to expected progression, signs, or symptoms of COVID-19, unless more severe than expected for the participant's current clinical status and medical history, were reported as a disease related events.
Time frame: Up to Week 12
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Number of Participants With Any Disease Related Events Through Week 12 | 4 Participants |
Secondary
Safety Sub-study: Number of Participants With Any Infusion-related Reaction Including Hypersensitivity 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. AESI is infusion-related reaction including hypersensitivity.
Time frame: Up to Week 12
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Number of Participants With Any Infusion-related Reaction Including Hypersensitivity Through Week 12 | 0 Participants |
Secondary
Safety Sub-study: Number of Participants With Non-SAEs 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 no serious, were considered as non-SAEs.
Time frame: Up to Week 12
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Number of Participants With Non-SAEs Through Week 12 | 0 Participants |
Secondary
Safety Sub-study: Number of Participants With Positive Neutralizing Antibodies
Blood samples were collected for the determination of positive neutralizing antibodies. A neutralizing antibody assay was performed. Neutralizing antibody test was only carried out for participants who have had a positive confirmatory binding antibody test result at visit. A participant was considered positive if they had at least one positive post-Baseline neutralizing antibody result.
Time frame: Up to Week 24
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Number of Participants With Positive Neutralizing Antibodies | 0 Participants |
Secondary
Safety Sub-study: Number of Participants With SAEs Through Week 36
An SAE is defined as any serious adverse event that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or any other situation according to medical or scientific judgement.
Time frame: Up to Week 36
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Number of Participants With SAEs Through Week 36 | 1 Participants |
Secondary
Safety Sub-study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody Through Week 24
Serum samples were collected for the determination of anti-drug antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample.
Time frame: Up to Week 24
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Number of Participants With Treatment-emergent Positive Anti-drug Antibody Through Week 24 | 3 Participants |
Secondary
Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab.
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 1, Pre-dose | NA Microgram per mL | — |
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 1, End of Infusion | 709.18 Microgram per mL | Geometric Coefficient of Variation 40.19 |
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 3 | 428.75 Microgram per mL | Geometric Coefficient of Variation 37.94 |
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 5 | 343.51 Microgram per mL | Geometric Coefficient of Variation 35.31 |
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 8 | 289.16 Microgram per mL | Geometric Coefficient of Variation 36.24 |
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 15 | 239.79 Microgram per mL | Geometric Coefficient of Variation 35.37 |
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration | Day 29 | 203.44 Microgram per mL | Geometric Coefficient of Variation 35.51 |
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration | Week 12 | 94.80 Microgram per mL | Geometric Coefficient of Variation 33.55 |
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration | Week 20 | 52.96 Microgram per mL | Geometric Coefficient of Variation 39.66 |
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Serum Concentration of Sotrovimab After Intravenous Administration | Week 24 | 40.82 Microgram per mL | Geometric Coefficient of Variation 37.08 |
Secondary
Safety Sub-study: Terminal Elimination Half-life of Sotrovimab After Intravenous Administration (t1/2)
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Terminal Elimination Half-life of Sotrovimab After Intravenous Administration (t1/2) | 59.432 Day |
Secondary
Safety Sub-study: Time to Reach Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Tmax)
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of Sotrovimab. Pharmacokinetic analysis of sotrovimab was conducted using non-compartmental method.
Time frame: Day 1: Pre-dose and end of infusion; Days 3, 5, 8, 15, 29 post-dose, Weeks 12, 20 and 24 post-dose
Population: Pharmacokinetic Population consisted of all participants in the Safety Population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values). Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Time to Reach Maximum Serum Concentration of Sotrovimab After Intravenous Administration (Tmax) | 0.044 Day |
Secondary
Safety Sub-study: Titers of Anti-drug Antibodies Against Sotrovimab Through Week 24
Confirmed positive ADA samples were further analyzed to obtain the titer of the antibodies. Titer is defined as the reciprocal of the highest dilution that yield results at or above the plate-based titer cut point x MRD. Titer Median and range from treatment emergent and unaffected are described below. Immunogenicity results were categorized as treatment- induced, treatment-boosted, and treatment-unaffected. Treatment-induced=those who are ADA negative or missing data at baseline and who have at least one post-dose ADA positive sample; Treatment boosted=those who are ADA positive at baseline and have a \>4\*Baseline titer; Treatment unaffected=those who are positive at baseline and post-Baseline titer \<=4\*Baseline titer or all post- Baseline negative. Treatment emergent = treatment induced or treatment boosted
Time frame: Up to Week 24
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Titers of Anti-drug Antibodies Against Sotrovimab Through Week 24 | Treatment-induced | 160.0 Titers |
| Main Study: Sotrovimab 500 mg IV | Safety Sub-study: Titers of Anti-drug Antibodies Against Sotrovimab Through Week 24 | Treatment-unaffected ADA | 160.0 Titers |