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CompletedNCT04988152Updated Jun 7, 2024Results posted

A Study to Investigate the PK, Safety, and Tolerability of Sotrovimab vs Placebo Administered IV or IM in Japanese and Caucasian Participants

A Phase 1 interventional study of sotrovimab and Placebo to Biologic in Covid19, sponsored by Vir Biotechnology, Inc.. Completed at 2 sites in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-06-07.

Sponsored by Vir Biotechnology, Inc. · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
48
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This is a Phase I single-dose study to investigate the pharmacokinetics, safety, and tolerability of sotrovimab vs placebo by intravenous or intramuscular administration in healthy Japanese and Caucasian participants.

Read the detailed description

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of a single fixed dose of sotrovimab administered intravenously (IV) or via intramuscular (IM) injection in Japanese and Caucasian healthy volunteers. This study will occur in two parts (Part 1 and Part 2).

Part 1: Healthy Japanese and Caucasian participants will be randomized in a 4:1 ratio to receive a single IV infusion of sotrovimab or volume-matched saline placebo on Day 1. Participants will be blinded to study intervention. Safety, tolerability, immunogenicity, and PK of IV sotrovimab will be evaluated.

Part 2: Healthy Japanese and Caucasian participants will be randomized in a 4:1 ratio to receive a single IM dose of sotrovimab or volume-matched saline placebo on Day 1. Participants will be blinded to study intervention. Safety, tolerability, immunogenicity, and PK of IM sotrovimab will be evaluated.

The data from this study will be used to supplement data available from other clinical trials that were conducted in non-Japanese participants.

02

Conditions studied

  • Covid19

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Keywords

  • SARS-CoV-2 coronavirus
  • coronavirus disease 2019
  • COVID-19
  • Japanese pharmacokinetics
03

In context

COVID-19

7,641 studies on the registry are indexed under COVID-19; 487 are open to participants now.

This study's enrollment of 48 is below the median of 100 across 4,100 interventional studies indexed under COVID-19.

Browse COVID-19 studies →

Lead sponsor

Vir Biotechnology, Inc. is the lead sponsor of 21 studies on the registry; 2 are open to participants now.

Of its 14 completed or terminated interventional studies of FDA-regulated products, 10 (71%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Male or female participants, aged 18 to 65 years, inclusive
  • Participants who are healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
  • Japanese participants must be of Japanese ancestry, defined as having been born in Japan, being descendants of four ethnic Japanese grandparents and two ethnic Japanese parents, holding a Japanese passport or identity papers, and being able to speak Japanese. Participants should have lived outside Japan for fewer than 10 years at the time of Screening.
  • Caucasian participants must be of Caucasian ancestry, defined as Caucasian descent as evidenced by appearance and verbal confirmation of familial heritage.
  • Body mass index (BMI) within the range of 18 to 29.9 kg/m2 (inclusive).
  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and protocol.

Exclusion criteria

Exclusion Criteria:

  • History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
  • Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
  • Breast cancer within the past 10 years.
  • Abnormal blood pressure at Screening.
  • Significant allergies to humanized monoclonal antibodies.
  • Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Use of any prescription medications (besides contraceptive medications or devices) within the 28 days prior to dosing or concomitantly, unless permitted by the protocol or approved by the Investigator in conjunction with the GSK medical monitor.
  • Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
  • Receipt of convalescent plasma from a recovered COVID-19 patient or anti-SARSCoV- 2 mAb within the last 3 months.
  • Receipt of any vaccine within 48 hours prior to enrollment. Vaccination will not be allowed for 90 days after dosing.
  • Participant has received a SARS-CoV-2 vaccine but has not completed all doses in the series more than 28 days prior to Screening
  • Participation in the study would result in loss of blood or blood products in excess of 500 mL within a 56 day period.
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Enrollment in any investigational vaccine study within the last 180 days or any other investigational drug study within 30 days prior to Day 1 or within 5 half-lives of the investigational compound, whichever is longer.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 prior to dosing.
  • Positive pre-study drug/alcohol screen.
  • Positive HIV antibody test.
  • History of regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of >14 units. One unit is equivalent to 8 g of alcohol: a half pint (\~240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
  • Regular use of known drugs of abuse.
05

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
48 participants (actual)

Study arms

  • Experimental
    Part 1 Sotrovimab intravenous infusion, single dose

    Biological: sotrovimab

  • Placebo comparator
    Part 1 Volume-matched placebo, intravenous infusion

    Other: Placebo to Biologic

  • Experimental
    Part 2 Sotrovimab intramuscular injection, single dose

    Biological: sotrovimab

  • Placebo comparator
    Part 2 Volume-matched placebo, intramuscular injection

    Other: Placebo to Biologic

Interventions

  • Biologicalsotrovimab

    sotrovimab IV infusion, single dose

  • OtherPlacebo to Biologic

    Sterile 0.9% (w/v) sodium chloride solution

  • Biologicalsotrovimab

    Sotrovimab IM injection, single dose

  • OtherPlacebo to Biologic

    Sterile 0.9% (w/v) sodium chloride solution

06

What researchers measure

Primary outcomes

  1. Part 1: Maximum Observed Serum Concentration (Cmax) of Sotrovimab Through Day 29

    The Cmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric means and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using analysis of covariance (ANCOVA) adjusting for body weight. The geometric Least Square (LS) means ratio (Japanese versus Caucasian) for Cmax and 90 percent (%) confidence interval (CI) are presented.

    Time frame: Day 1: Pre-dose, at end of infusion (EOI) and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Days 8, 15 and 29

  2. Part 1: Area Under the Serum-concentration Time Curve From Day 1 to Day 29 (AUC[D1-29]) of Sotrovimab

    The AUC (D1-29) was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for AUC(D1-29) and 90% Confidence Interval are presented.

    Time frame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Days 8, 15 and 29

  3. Part 1: Time to Cmax (Tmax) of Sotrovimab Through Day 29

    The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

    Time frame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Days 8, 15 and 29

  4. Part 1: Concentration at Day 29 (CD29) Following Administration of Sotrovimab

    The CD29 was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented.

    Time frame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Days 8, 15 and 29

  5. Part 2: Cmax of Sotrovimab Through Day 29

    The Cmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for Cmax and 90% confidence interval are presented.

    Time frame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Days 8, 15 and 29

  6. Part 2: AUC(D1-29) of Sotrovimab

    The AUC (D1-29) was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for AUC(D1-29) and 90% confidence interval are presented.

    Time frame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Days 8, 15 and 29

  7. Part 2: Tmax of Sotrovimab Through Day 29

    The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

    Time frame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Days 8, 15 and 29

  8. Part 2: CD29 of Sotrovimab

    The CD29 was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented.

    Time frame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Days 8, 15 and 29

  9. Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29

    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. 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 situations as per medical or scientific judgment. Adverse events which were not serious adverse events were considered as Non-Serious adverse events.

    Time frame: Up to Day 29

  10. Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29

    Adverse events of special interest (AESI) are relevant known toxicities of other therapeutic monoclonal antibodies (mAbs) or signals observed in nonclinical programs of sotrovimab. AESI were defined as Infusion-related reactions (IRR) including hypersensitivity reactions, Hypersensitivity Standardized Medical dictionary for Regulatory Activities (MedDRA) Queries (SMQ) narrow, Infusion site reactions, Immunogenicity related adverse drug reactions (ADR) and AE potentially related to antibody-dependent enhancement of disease (ADE). Only IRR including hypersensitivity and Infusion site reactions through Day 29 were summarized.

    Time frame: Up to Day 29

  11. Part 1: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings Through Day 29

    Twelve-lead ECG's were obtained in the semi-recumbent or supine position after 10 minutes of rest using an ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant worst case post-Baseline ECG findings were reported.

    Time frame: Up to Day 29

  12. Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29

    Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a semi-supine or sitting position after 5 minutes rest. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

    Time frame: Baseline (Day 1) and up to Day 29

  13. Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29

    Blood samples were collected for analysis of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Glucose (fasting) and Glucose. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome (AIDS) Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

    Time frame: Baseline (Day 1) and up to Day 29

  14. Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29

    Urine samples were collected for analysis of bilirubin, leukocyte esterase, occult blood, and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Baseline is defined as the latest pre-dose assessment with a non-missing value on or after Day -1 visit, including those from unscheduled visits. Any increase means any increase to small, moderate, severe, potentially life threatening or positive post-Baseline relative to Baseline. Data is presented for only those parameters for which participants had any increase in urinalysis results post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.

    Time frame: Baseline (Day 1) and up to Day 29

  15. Part 2: Number of Participants With SAE and Common Non-SAE Through Day 29

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. 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 situations as per medical or scientific judgment. Adverse events which were not serious adverse events were considered as Non-Serious adverse events.

    Time frame: Part 2: Number of participants with SAE and common non-SAE through Day 29

  16. Part 2: Number of Participants With AESI Through Day 29

    Adverse events of special interest (AESI) are relevant known toxicities of other therapeutic mAbs or signals observed in nonclinical programs of sotrovimab. AESI were defined as Injection-related reactions including hypersensitivity reactions, Hypersensitivity (SMQ narrow), Injection site reactions, Immunogenicity related adverse drug reactions (ADR) and AE potentially related to antibody-dependent enhancement of disease (ADE). Only Injection-related reactions including hypersensitivity and Injection site reactions through Day 29 were summarized.

    Time frame: Up to Day 29

  17. Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Day 29

    Twelve-lead ECG's were obtained in the semi-recumbent or supine position after 10 minutes of rest using an ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant worst case post-Baseline ECG findings were reported.

    Time frame: Up to Day 29

  18. Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29

    Vital signs including SBP, DBP and pulse rate were measured in a semi-supine or sitting position after 5 minutes rest. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Worst-case post-Baseline shift data is presented.

    Time frame: Baseline (Day) and up to Day 29

  19. Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29

    Blood samples were collected for analysis of clinical chemistry parameters including Alkaline Phosphatase (ALP), Total Bilirubin, Glucose, Potassium and Sodium. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome (AIDS) Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

    Time frame: Baseline (Day 1) and up to Day 29

  20. Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29

    Urine samples were collected for analysis of bilirubin, glucose, leukocyte esterase, occult blood and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Baseline is defined as the latest pre-dose assessment with a non-missing value on or after Day -1 visit, including those from unscheduled visits. Any increase means any increase to small, moderate, severe, potentially life threatening or positive post-Baseline relative to Baseline. Data is presented for only those parameters for which participants had any increase in urinalysis results post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.

    Time frame: Baseline (Day 1) and up to Day 29

Secondary outcomes

  1. Part 1: Cmax of Sotrovimab Through Week 18

    The Cmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for Cmax and 90% confidence interval are presented.

    Time frame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18

  2. Part 1: Area Under the Serum Concentration-time Curve Extrapolated to Infinite Time (AUC[0-infinity]) of Sotrovimab Through Week 18

    The AUC(0-infinity) was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented.

    Time frame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18

  3. Part 1: Area Under the Curve From the Time of Dosing to the Time of the Last Measurable (Positive) Concentration (AUClast) of Sotrovimab Through Week 18

    The AUClast was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for AUClast and 90% Confidence Interval are presented.

    Time frame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18

  4. Part 1: Tmax of Sotrovimab Through Week 18

    The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

    Time frame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18

  5. Part 1: Time of the Last Quantifiable Concentration (Tlast) of Sotrovimab Through Week 18

    The Tlast was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

    Time frame: Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18

  6. Part 1: Terminal Elimination Half-life (t1/2) of Sotrovimab Through Week 18

    The T1/2 was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

    Time frame: Weeks 2, 3, 4, 6, 8, 12 and 18

  7. Part 2: Cmax of Sotrovimab Through Week 18

    The Cmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for Cmax and 90% Confidence Interval are presented.

    Time frame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18

  8. Part 2: AUC(0-infinity) of Sotrovimab Through Week 18

    The AUC0-infinity was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented.

    Time frame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18

  9. Part 2: AUClast of Sotrovimab Through Week 18

    The AUClast was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for AUClast and 90% Confidence Interval are presented.

    Time frame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18

  10. Part 2: Tmax of Sotrovimab Through Week 18

    The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

    Time frame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18

  11. Part 2: Tlast of Sotrovimab Through Week 18

    The Tlast was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

    Time frame: Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18

  12. Part 2: T1/2 of Sotrovimab Through Week 18

    The T1/2 was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

    Time frame: Weeks 2, 3, 4, 6, 8, 12 and 18

  13. Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18

    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. 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 situations as per medical or scientific judgment. Adverse events which were not serious adverse events were considered as Non-Serious adverse events.

    Time frame: Up to Week 18

  14. Part 1: Number of Participants With AESI Through Week 18

    Adverse events of special interest (AESI) are relevant known toxicities of other therapeutic mAbs or signals observed in nonclinical programs of sotrovimab. AESI were defined as Infusion-related reactions (IRR) including hypersensitivity reactions, Hypersensitivity (SMQ narrow), Infusion site reactions, Immunogenicity related adverse drug reactions (ADR) and AE potentially related to antibody-dependent enhancement of disease (ADE).

    Time frame: Up to Week 18

  15. Part 1: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18

    Twelve-lead ECG's were obtained in the semi-recumbent or supine position after 10 minutes of rest using an ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant worst case post-Baseline ECG findings were reported.

    Time frame: Up to Week 18

  16. Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18

    Vital signs including SBP, DBP and pulse rate were measured in a semi-supine or sitting position after 5 minutes rest. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

    Time frame: Baseline (Day 1) and up to Week 18

  17. Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18

    Blood samples were collected for analysis of clinical chemistry parameters including Aspartate Aminotransferase (AST), Total Bilirubin, Direct Bilirubin, Glucose (fasting), Glucose and Sodium. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome (AIDS) Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

    Time frame: Baseline (Day 1) and up to Week 18

  18. Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18

    Urine samples were collected for analysis of bilirubin, leukocyte esterase, occult blood and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Baseline is defined as the latest pre-dose assessment with a non-missing value on or after Day -1 visit, including those from unscheduled visits. Any increase means any increase to small, moderate, severe, potentially life threatening or positive post-Baseline relative to Baseline. Data is presented for only those parameters for which participants had any increase in urinalysis results post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.

    Time frame: Baseline (Day 1) and up to Week 18

  19. Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18

    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. 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 situations as per medical or scientific judgment. Adverse events which were not serious adverse events were considered as Non-Serious adverse events.

    Time frame: Up to Week 18

  20. Part 2: Number of Participants With AESI Through Week 18

    Adverse events of special interest (AESI) are relevant known toxicities of other therapeutic mAbs or signals observed in nonclinical programs of sotrovimab. AESI were defined as Injection-related reactions including hypersensitivity reactions, Hypersensitivity (SMQ narrow), Injection site reactions, Immunogenicity related adverse drug reactions (ADR) and AE potentially related to antibody-dependent enhancement of disease (ADE).

    Time frame: Up to Week 18

  21. Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18

    Twelve 12-lead ECG's were obtained in the semi-recumbent or supine position after 10 minutes of rest using an ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant worst case post-Baseline ECG findings were reported.

    Time frame: Up to Week 18

  22. Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18

    Vital signs including SBP, DBP and pulse rate were measured in a semi-supine or sitting position after 5 minutes rest. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

    Time frame: Baseline (Day 1) and up to Week 18

  23. Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18

    Blood samples were collected for analysis of clinical chemistry parameters including Alanine aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Total Bilirubin, Creatinine, Glucose (fasting), Glucose, Potassium and Sodium. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

    Time frame: Baseline (Day 1) and up to Week 18

  24. Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18

    Urine samples were collected for analysis of bilirubin, glucose, leukocyte esterase, nitrite, occult blood, protein and urobilinogen by a dipstick method. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Baseline is defined as the latest pre-dose assessment with a non-missing value on or after Day -1 visit, including those from unscheduled visits. Any increase means any increase to small, moderate, severe, potentially life threatening or positive post-Baseline relative to Baseline. Data is presented for only those parameters for which participants had any increase in urinalysis results post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.

    Time frame: Baseline (Day 1) and up to Week 18

Other outcomes

  1. Part 1 and Part 2: Bioavailability of Sotrovimab IM Versus IV Formulation Using AUClast

    Bioavailability of Sotrovimab was estimated using ANCOVA model with AUClast as dependent variable and ethnicity, body weight, route of administration as covariates with all available data (Part 1 \[IV\] and Part 2 \[IM\]) of Sotrovimab concentrations in serum. The AUClast Geometric Least Squares (LS) Means were estimated for each formulation and then a single parameter reported as the ratio of the AUClast geometric LS means (IM/IV) along with the 90% Confidence Interval were calculated. A single ratio parameter derived using the Geometric LS Means of AUClast IM versus IV and associated 90% Confidence Interval are presented.

    Time frame: Part 1: Day 1 (Pre-dose, at end of infusion and 1,2,6,8,24 [Day 2] and 48 [Day 3] hours after end of infusion); Weeks 2,3,4,6,8,12,18; Part 2: Day 1(Pre-dose and 1,2,6,8,24 [Day 2] and 48 [Day 3] hours after first IM injection); Weeks 2,3,4, 6,8,12,18

07

Results

Posted Jun 7, 2024

Participant flow

This study was conducted in the United States.

Part 1 (Up to Week 18)
Participant flow — Part 1 (Up to Week 18)
MilestonePart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)Part 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Started33990000
Completed33990000
Not completed00000000
Part 2 (Up to Week 18)
Participant flow — Part 2 (Up to Week 18)
MilestonePart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)Part 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Started0000221010
Completed0000221010
Not completed00000000

Outcome measures

PrimaryPart 1: Maximum Observed Serum Concentration (Cmax) of Sotrovimab Through Day 29

The Cmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric means and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using analysis of covariance (ANCOVA) adjusting for body weight. The geometric Least Square (LS) means ratio (Japanese versus Caucasian) for Cmax and 90 percent (%) confidence interval (CI) are presented.

Time frame:
Day 1: Pre-dose, at end of infusion (EOI) and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Days 8, 15 and 29
Reported as:
Geometric mean · Micrograms per milliliter
Part 1: Maximum Observed Serum Concentration (Cmax) of Sotrovimab Through Day 29
Micrograms per milliliterPart 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Maximum Observed Serum Concentration (Cmax) of Sotrovimab Through Day 29238.32 ± 18.5188.66 ± 13.8
Statistical analysis
  • Part 1: Sotrovimab 500 mg IV (Japanese) vs Part 1: Sotrovimab 500 mg IV (Caucasian) · Ratio of geometric least squares means: 1.0724 · 90% CI 0.8519 to 1.3500The ratio of geometric LS means and 90% confidence intervals were obtained from ANCOVA model, with Cmax as the dependent variable, and ethnicity and body weight were covariates.
PrimaryPart 1: Area Under the Serum-concentration Time Curve From Day 1 to Day 29 (AUC[D1-29]) of Sotrovimab

The AUC (D1-29) was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for AUC(D1-29) and 90% Confidence Interval are presented.

Time frame:
Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Days 8, 15 and 29
Reported as:
Geometric mean · Day*micrograms per milliliter
Part 1: Area Under the Serum-concentration Time Curve From Day 1 to Day 29 (AUC[D1-29]) of Sotrovimab
Day*micrograms per milliliterPart 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Area Under the Serum-concentration Time Curve From Day 1 to Day 29 (AUC[D1-29]) of Sotrovimab2699.29 ± 11.52154.90 ± 9.0
Statistical analysis
  • Part 1: Sotrovimab 500 mg IV (Japanese) vs Part 1: Sotrovimab 500 mg IV (Caucasian) · Ratio of geometric least squares means: 1.0513 · 90% CI 0.9281 to 1.1908The ratio of geometric LS means and 90% confidence intervals were obtained from ANCOVA model, with AUC(D1-29) as the dependent variable, and ethnicity and body weight were covariates.
PrimaryPart 1: Time to Cmax (Tmax) of Sotrovimab Through Day 29

The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

Time frame:
Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Days 8, 15 and 29
Reported as:
Median · Hours
Part 1: Time to Cmax (Tmax) of Sotrovimab Through Day 29
HoursPart 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Time to Cmax (Tmax) of Sotrovimab Through Day 291.567 (1.55 to 6.55)0.733 (0.68 to 1.58)
PrimaryPart 1: Concentration at Day 29 (CD29) Following Administration of Sotrovimab

The CD29 was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented.

Time frame:
Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Days 8, 15 and 29
Reported as:
Geometric mean · Micrograms per milliliter
Part 1: Concentration at Day 29 (CD29) Following Administration of Sotrovimab
Micrograms per milliliterPart 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Concentration at Day 29 (CD29) Following Administration of Sotrovimab71.48 ± 15.155.56 ± 9.1
PrimaryPart 2: Cmax of Sotrovimab Through Day 29

The Cmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for Cmax and 90% confidence interval are presented.

Time frame:
Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Days 8, 15 and 29
Reported as:
Geometric mean · Micrograms per milliliter
Part 2: Cmax of Sotrovimab Through Day 29
Micrograms per milliliterPart 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Part 2: Cmax of Sotrovimab Through Day 2960.33 ± 32.032.27 ± 50.4
Statistical analysis
  • Part 2: Sotrovimab 500 mg IM (Japanese) vs Part 2: Sotrovimab 500 mg IM (Caucasian) · Ratio of geometric least squares means: 1.6999 · 90% CI 1.1500 to 2.5129The ratio of geometric LS means and 90% confidence intervals were obtained from ANCOVA model, with Cmax as the dependent variable, and ethnicity and body weight were covariates.
PrimaryPart 2: AUC(D1-29) of Sotrovimab

The AUC (D1-29) was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for AUC(D1-29) and 90% confidence interval are presented.

Time frame:
Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Days 8, 15 and 29
Reported as:
Geometric mean · Day*micrograms per milliliter
Part 2: AUC(D1-29) of Sotrovimab
Day*micrograms per milliliterPart 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Part 2: AUC(D1-29) of Sotrovimab1378.28 ± 28.1743.39 ± 46.4
Statistical analysis
  • Part 2: Sotrovimab 500 mg IM (Japanese) vs Part 2: Sotrovimab 500 mg IM (Caucasian) · Ratio of geometric least squares means: 1.5869 · 90% CI 1.1236 to 2.2413The ratio of geometric LS means and 90% confidence intervals were obtained from ANCOVA model, with AUC(D1-29) as the dependent variable, and ethnicity and body weight were covariates.
PrimaryPart 2: Tmax of Sotrovimab Through Day 29

The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

Time frame:
Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Days 8, 15 and 29
Reported as:
Median · Hours
Part 2: Tmax of Sotrovimab Through Day 29
HoursPart 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Part 2: Tmax of Sotrovimab Through Day 29168.88 (167.8 to 334.1)166.60 (165.4 to 696.4)
PrimaryPart 2: CD29 of Sotrovimab

The CD29 was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented.

Time frame:
Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Days 8, 15 and 29
Reported as:
Geometric mean · Micrograms per milliliter
Part 2: CD29 of Sotrovimab
Micrograms per milliliterPart 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Part 2: CD29 of Sotrovimab44.5 ± 30.529.14 ± 50.9
PrimaryPart 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. 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 situations as per medical or scientific judgment. Adverse events which were not serious adverse events were considered as Non-Serious adverse events.

Time frame:
Up to Day 29
Reported as:
Count of participants · Participants
Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29
ParticipantsPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
SAE0000
Non-SAE1121
PrimaryPart 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29

Adverse events of special interest (AESI) are relevant known toxicities of other therapeutic monoclonal antibodies (mAbs) or signals observed in nonclinical programs of sotrovimab. AESI were defined as Infusion-related reactions (IRR) including hypersensitivity reactions, Hypersensitivity Standardized Medical dictionary for Regulatory Activities (MedDRA) Queries (SMQ) narrow, Infusion site reactions, Immunogenicity related adverse drug reactions (ADR) and AE potentially related to antibody-dependent enhancement of disease (ADE). Only IRR including hypersensitivity and Infusion site reactions through Day 29 were summarized.

Time frame:
Up to Day 29
Reported as:
Count of participants · Participants
Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29
ParticipantsPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
IRR including hypersensitivity0000
Infusion Site Reactions0000
PrimaryPart 1: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings Through Day 29

Twelve-lead ECG's were obtained in the semi-recumbent or supine position after 10 minutes of rest using an ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant worst case post-Baseline ECG findings were reported.

Time frame:
Up to Day 29
Reported as:
Count of participants · Participants
Part 1: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings Through Day 29
ParticipantsPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings Through Day 290000
PrimaryPart 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29

Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a semi-supine or sitting position after 5 minutes rest. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

Time frame:
Baseline (Day 1) and up to Day 29
Reported as:
Count of participants · Participants
Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29
ParticipantsPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 290000
PrimaryPart 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29

Blood samples were collected for analysis of clinical chemistry parameters including Total Bilirubin, Direct Bilirubin, Glucose (fasting) and Glucose. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome (AIDS) Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

Time frame:
Baseline (Day 1) and up to Day 29
Reported as:
Count of participants · Participants
Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29
ParticipantsPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Total Bilirubin, High, Grade 0 to Grade 10110
Direct Bilirubin, High, Grade 0 to Grade 30010
Glucose (fasting), High, Grade 0 to Grade 10002
Glucose (fasting), High, Grade 0 to Grade 20001
Glucose, Low, Grade 1 to Grade 00100
PrimaryPart 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29

Urine samples were collected for analysis of bilirubin, leukocyte esterase, occult blood, and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Baseline is defined as the latest pre-dose assessment with a non-missing value on or after Day -1 visit, including those from unscheduled visits. Any increase means any increase to small, moderate, severe, potentially life threatening or positive post-Baseline relative to Baseline. Data is presented for only those parameters for which participants had any increase in urinalysis results post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.

Time frame:
Baseline (Day 1) and up to Day 29
Reported as:
Count of participants · Participants
Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29
ParticipantsPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Bilirubin1020
Leukocyte Esterase0020
Occult Blood0032
Protein0010
PrimaryPart 2: Number of Participants With SAE and Common Non-SAE Through Day 29

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. 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 situations as per medical or scientific judgment. Adverse events which were not serious adverse events were considered as Non-Serious adverse events.

Time frame:
Part 2: Number of participants with SAE and common non-SAE through Day 29
Reported as:
Count of participants · Participants
Part 2: Number of Participants With SAE and Common Non-SAE Through Day 29
ParticipantsPart 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
SAE0000
Non-SAE0142
PrimaryPart 2: Number of Participants With AESI Through Day 29

Adverse events of special interest (AESI) are relevant known toxicities of other therapeutic mAbs or signals observed in nonclinical programs of sotrovimab. AESI were defined as Injection-related reactions including hypersensitivity reactions, Hypersensitivity (SMQ narrow), Injection site reactions, Immunogenicity related adverse drug reactions (ADR) and AE potentially related to antibody-dependent enhancement of disease (ADE). Only Injection-related reactions including hypersensitivity and Injection site reactions through Day 29 were summarized.

Time frame:
Up to Day 29
Reported as:
Count of participants · Participants
Part 2: Number of Participants With AESI Through Day 29
ParticipantsPart 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Injection-related reactions including hypersensitivity0000
Injection Site Reaction0010
PrimaryPart 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Day 29

Twelve-lead ECG's were obtained in the semi-recumbent or supine position after 10 minutes of rest using an ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant worst case post-Baseline ECG findings were reported.

Time frame:
Up to Day 29
Reported as:
Count of participants · Participants
Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Day 29
ParticipantsPart 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Day 290000
PrimaryPart 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29

Vital signs including SBP, DBP and pulse rate were measured in a semi-supine or sitting position after 5 minutes rest. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Worst-case post-Baseline shift data is presented.

Time frame:
Baseline (Day) and up to Day 29
Reported as:
Count of participants · Participants
Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29
ParticipantsPart 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
DBP; Grade 0 to Grade 10000
SBP; Grade 1 to Grade 00010
Pulse rate; Grade 0 to Grade 10000
PrimaryPart 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29

Blood samples were collected for analysis of clinical chemistry parameters including Alkaline Phosphatase (ALP), Total Bilirubin, Glucose, Potassium and Sodium. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome (AIDS) Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

Time frame:
Baseline (Day 1) and up to Day 29
Reported as:
Count of participants · Participants
Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29
ParticipantsPart 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
ALP, High, Grade 0 to Grade 10001
Total Bilirubin, High, Grade 0 to Grade 10010
Glucose, Low, Grade 0 to Grade 11000
Potassium, High, Grade 0 to Grade 40010
Sodium, Low, Grade 1 to Grade 10011
PrimaryPart 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29

Urine samples were collected for analysis of bilirubin, glucose, leukocyte esterase, occult blood and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Baseline is defined as the latest pre-dose assessment with a non-missing value on or after Day -1 visit, including those from unscheduled visits. Any increase means any increase to small, moderate, severe, potentially life threatening or positive post-Baseline relative to Baseline. Data is presented for only those parameters for which participants had any increase in urinalysis results post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.

Time frame:
Baseline (Day 1) and up to Day 29
Reported as:
Count of participants · Participants
Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29
ParticipantsPart 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Bilirubin1000
Glucose0010
Leukocyte Esterase0012
Occult Blood1114
Protein0012
SecondaryPart 1: Cmax of Sotrovimab Through Week 18

The Cmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for Cmax and 90% confidence interval are presented.

Time frame:
Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18
Reported as:
Geometric mean · Micrograms per milliliter
Part 1: Cmax of Sotrovimab Through Week 18
Micrograms per milliliterPart 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Cmax of Sotrovimab Through Week 18238.32 ± 18.5188.66 ± 13.8
Statistical analysis
  • Part 1: Sotrovimab 500 mg IV (Japanese) vs Part 1: Sotrovimab 500 mg IV (Caucasian) · Ratio of geometric least squares means: 1.0724 · 90% CI 0.8519 to 1.3500The ratio of geometric LS means and 90% confidence intervals were obtained from ANCOVA model, with Cmax as the dependent variable, and ethnicity and body weight were covariates.
SecondaryPart 1: Area Under the Serum Concentration-time Curve Extrapolated to Infinite Time (AUC[0-infinity]) of Sotrovimab Through Week 18

The AUC(0-infinity) was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented.

Time frame:
Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18
Reported as:
Geometric mean · Day*micrograms per milliliter
Part 1: Area Under the Serum Concentration-time Curve Extrapolated to Infinite Time (AUC[0-infinity]) of Sotrovimab Through Week 18
Day*micrograms per milliliterPart 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Area Under the Serum Concentration-time Curve Extrapolated to Infinite Time (AUC[0-infinity]) of Sotrovimab Through Week 187513.23 ± 22.15388.17 ± 30.8
SecondaryPart 1: Area Under the Curve From the Time of Dosing to the Time of the Last Measurable (Positive) Concentration (AUClast) of Sotrovimab Through Week 18

The AUClast was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for AUClast and 90% Confidence Interval are presented.

Time frame:
Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18
Reported as:
Geometric mean · Day*micrograms per milliliter
Part 1: Area Under the Curve From the Time of Dosing to the Time of the Last Measurable (Positive) Concentration (AUClast) of Sotrovimab Through Week 18
Day*micrograms per milliliterPart 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Area Under the Curve From the Time of Dosing to the Time of the Last Measurable (Positive) Concentration (AUClast) of Sotrovimab Through Week 186597.35 ± 10.95098.64 ± 12.0
Statistical analysis
  • Part 1: Sotrovimab 500 mg IV (Japanese) vs Part 1: Sotrovimab 500 mg IV (Caucasian) · Ratio of geometric least squares means: 1.0673 · 90% CI 0.9286 to 1.2268The ratio of geometric LS means and 90% confidence intervals were obtained from ANCOVA model, with AUClast as the dependent variable, and ethnicity and body weight were covariates.
SecondaryPart 1: Tmax of Sotrovimab Through Week 18

The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

Time frame:
Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18
Reported as:
Median · Day
Part 1: Tmax of Sotrovimab Through Week 18
DayPart 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Tmax of Sotrovimab Through Week 180.065 (0.06 to 0.27)0.031 (0.03 to 0.07)
SecondaryPart 1: Time of the Last Quantifiable Concentration (Tlast) of Sotrovimab Through Week 18

The Tlast was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

Time frame:
Day 1: Pre-dose, at end of infusion and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after end of infusion; Weeks 2, 3, 4, 6, 8, 12 and 18
Reported as:
Median · Day
Part 1: Time of the Last Quantifiable Concentration (Tlast) of Sotrovimab Through Week 18
DayPart 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Time of the Last Quantifiable Concentration (Tlast) of Sotrovimab Through Week 18125.98 (119.0 to 126.1)125.98 (125.0 to 127.1)
SecondaryPart 1: Terminal Elimination Half-life (t1/2) of Sotrovimab Through Week 18

The T1/2 was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

Time frame:
Weeks 2, 3, 4, 6, 8, 12 and 18
Reported as:
Median · Day
Part 1: Terminal Elimination Half-life (t1/2) of Sotrovimab Through Week 18
DayPart 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Terminal Elimination Half-life (t1/2) of Sotrovimab Through Week 1856.38 (40.9 to 65.7)58.85 (33.6 to 113.6)
SecondaryPart 2: Cmax of Sotrovimab Through Week 18

The Cmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for Cmax and 90% Confidence Interval are presented.

Time frame:
Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18
Reported as:
Geometric mean · Micrograms per milliliter
Part 2: Cmax of Sotrovimab Through Week 18
Micrograms per milliliterPart 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Part 2: Cmax of Sotrovimab Through Week 1860.33 ± 32.032.27 ± 50.4
Statistical analysis
  • Part 2: Sotrovimab 500 mg IM (Japanese) vs Part 2: Sotrovimab 500 mg IM (Caucasian) · Ratio of geometric least squares means: 1.6999 · 90% CI 1.1500 to 2.5129The ratio of geometric LS means and 90% confidence intervals were obtained from ANCOVA model, with Cmax as the dependent variable, and ethnicity and body weight were covariates.
SecondaryPart 2: AUC(0-infinity) of Sotrovimab Through Week 18

The AUC0-infinity was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented.

Time frame:
Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18
Reported as:
Geometric mean · Day*micrograms per milliliter
Part 2: AUC(0-infinity) of Sotrovimab Through Week 18
Day*micrograms per milliliterPart 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Part 2: AUC(0-infinity) of Sotrovimab Through Week 185687.48 ± NA2788.57 ± 60.9
SecondaryPart 2: AUClast of Sotrovimab Through Week 18

The AUClast was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. An ethnicity comparison (Japanese versus Caucasian) was also conducted using ANCOVA adjusting for body weight. The geometric LS means ratio (Japanese versus Caucasian) for AUClast and 90% Confidence Interval are presented.

Time frame:
Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18
Reported as:
Geometric mean · Day*micrograms per milliliter
Part 2: AUClast of Sotrovimab Through Week 18
Day*micrograms per milliliterPart 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Part 2: AUClast of Sotrovimab Through Week 184018.36 ± 25.12148.93 ± 39.6
Statistical analysis
  • Part 2: Sotrovimab 500 mg IM (Japanese) vs Part 2: Sotrovimab 500 mg IM (Caucasian) · Ratio of geometric least squares means: 1.5766 · 90% CI 1.1777 to 2.1106The ratio of geometric LS means and 90% confidence intervals were obtained from ANCOVA model, with AUClast as the dependent variable, and ethnicity and body weight were covariates
SecondaryPart 2: Tmax of Sotrovimab Through Week 18

The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

Time frame:
Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18
Reported as:
Median · Day
Part 2: Tmax of Sotrovimab Through Week 18
DayPart 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Part 2: Tmax of Sotrovimab Through Week 187.04 (7.0 to 13.9)6.94 (6.9 to 29.0)
SecondaryPart 2: Tlast of Sotrovimab Through Week 18

The Tlast was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

Time frame:
Day 1: Pre-dose and 1, 2, 6, 8, 24 (Day 2) and 48 (Day 3) hours after first IM injection; Weeks 2, 3, 4, 6, 8, 12 and 18
Reported as:
Median · Day
Part 2: Tlast of Sotrovimab Through Week 18
DayPart 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Part 2: Tlast of Sotrovimab Through Week 18127.54 (125.9 to 129.0)125.52 (118.9 to 132.0)
SecondaryPart 2: T1/2 of Sotrovimab Through Week 18

The T1/2 was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.

Time frame:
Weeks 2, 3, 4, 6, 8, 12 and 18
Reported as:
Median · Day
Part 2: T1/2 of Sotrovimab Through Week 18
DayPart 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Part 2: T1/2 of Sotrovimab Through Week 1867.28 (53.2 to 85.5)67.40 (48.6 to 89.2)
SecondaryPart 1: Number of Participants With SAE and Common Non-SAE Through Week 18

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. 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 situations as per medical or scientific judgment. Adverse events which were not serious adverse events were considered as Non-Serious adverse events.

Time frame:
Up to Week 18
Reported as:
Count of participants · Participants
Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18
ParticipantsPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
SAE0000
Non-SAE1121
SecondaryPart 1: Number of Participants With AESI Through Week 18

Adverse events of special interest (AESI) are relevant known toxicities of other therapeutic mAbs or signals observed in nonclinical programs of sotrovimab. AESI were defined as Infusion-related reactions (IRR) including hypersensitivity reactions, Hypersensitivity (SMQ narrow), Infusion site reactions, Immunogenicity related adverse drug reactions (ADR) and AE potentially related to antibody-dependent enhancement of disease (ADE).

Time frame:
Up to Week 18
Reported as:
Count of participants · Participants
Part 1: Number of Participants With AESI Through Week 18
ParticipantsPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
IRR including hypersensitivity0000
Hypersensitivity (SMQ narrow)0010
Infusion Site Reaction0000
Immunogenicity related ADR0000
AE potentially related to ADE0000
SecondaryPart 1: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18

Twelve-lead ECG's were obtained in the semi-recumbent or supine position after 10 minutes of rest using an ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant worst case post-Baseline ECG findings were reported.

Time frame:
Up to Week 18
Reported as:
Count of participants · Participants
Part 1: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18
ParticipantsPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 180000
SecondaryPart 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18

Vital signs including SBP, DBP and pulse rate were measured in a semi-supine or sitting position after 5 minutes rest. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

Time frame:
Baseline (Day 1) and up to Week 18
Reported as:
Count of participants · Participants
Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18
ParticipantsPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 180000
SecondaryPart 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18

Blood samples were collected for analysis of clinical chemistry parameters including Aspartate Aminotransferase (AST), Total Bilirubin, Direct Bilirubin, Glucose (fasting), Glucose and Sodium. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome (AIDS) Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

Time frame:
Baseline (Day 1) and up to Week 18
Reported as:
Count of participants · Participants
Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18
ParticipantsPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
AST, High, Grade 0 to Grade 20001
Total Bilirubin, High, Grade 0 to Grade 11100
Total Bilirubin, High, Grade 0 to Grade 20010
Direct Bilirubin, High, Grade 0 to Grade 30010
Glucose (fasting), High, Grade 0 to Grade 10003
Glucose (fasting), High, Grade 0 to Grade 20001
Glucose, Low, Grade 1 to Grade 00100
Sodium, Low, Grade 0 to Grade 10001
SecondaryPart 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18

Urine samples were collected for analysis of bilirubin, leukocyte esterase, occult blood and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Baseline is defined as the latest pre-dose assessment with a non-missing value on or after Day -1 visit, including those from unscheduled visits. Any increase means any increase to small, moderate, severe, potentially life threatening or positive post-Baseline relative to Baseline. Data is presented for only those parameters for which participants had any increase in urinalysis results post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.

Time frame:
Baseline (Day 1) and up to Week 18
Reported as:
Count of participants · Participants
Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18
ParticipantsPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)
Bilirubin1020
Leukocyte Esterase1131
Occult Blood1043
Protein1011
SecondaryPart 2: Number of Participants With SAE and Common Non-SAE Through Week 18

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. 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 situations as per medical or scientific judgment. Adverse events which were not serious adverse events were considered as Non-Serious adverse events.

Time frame:
Up to Week 18
Reported as:
Count of participants · Participants
Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18
ParticipantsPart 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
SAE0000
Non-SAE0143
SecondaryPart 2: Number of Participants With AESI Through Week 18

Adverse events of special interest (AESI) are relevant known toxicities of other therapeutic mAbs or signals observed in nonclinical programs of sotrovimab. AESI were defined as Injection-related reactions including hypersensitivity reactions, Hypersensitivity (SMQ narrow), Injection site reactions, Immunogenicity related adverse drug reactions (ADR) and AE potentially related to antibody-dependent enhancement of disease (ADE).

Time frame:
Up to Week 18
Reported as:
Count of participants · Participants
Part 2: Number of Participants With AESI Through Week 18
ParticipantsPart 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Injection related reaction including hypersensitivity0000
Hypersensitivity (SMQ narrow)0000
Injection Site Reaction0010
Immunogenicity related ADR0000
AE potentially related to ADE0000
SecondaryPart 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18

Twelve 12-lead ECG's were obtained in the semi-recumbent or supine position after 10 minutes of rest using an ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for the number of participants with abnormal clinically significant worst case post-Baseline ECG findings were reported.

Time frame:
Up to Week 18
Reported as:
Count of participants · Participants
Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18
ParticipantsPart 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 180000
SecondaryPart 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18

Vital signs including SBP, DBP and pulse rate were measured in a semi-supine or sitting position after 5 minutes rest. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

Time frame:
Baseline (Day 1) and up to Week 18
Reported as:
Count of participants · Participants
Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18
ParticipantsPart 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
DBP; Grade 0 to Grade 10010
SBP; Grade 1 to Grade 00010
SecondaryPart 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18

Blood samples were collected for analysis of clinical chemistry parameters including Alanine aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Total Bilirubin, Creatinine, Glucose (fasting), Glucose, Potassium and Sodium. Baseline is latest pre-dose assessment with a non-missing value on or after Day -1 visit including those from unscheduled visits. Grade Shift from Baseline is defined as shift from any grade (at Baseline) to Grades 1, 2, 3 and 4 post-Baseline. A worst post-Baseline grade shift is defined as worst change that occurred at any measured time point during treatment period. Grading was determined by the Division of Acquired Immunodeficiency Syndrome Table for Grading Severity (DAIDS) version 2.1. Grade 0=Normal, Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4= Potentially Life-Threatening. Data is presented for only those parameters for which participants had grade shifts from Baseline grade. Worst-case post-Baseline shift data is presented.

Time frame:
Baseline (Day 1) and up to Week 18
Reported as:
Count of participants · Participants
Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18
ParticipantsPart 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
ALT, High, Grade 0 to Grade 10001
ALP, High, Grade 0 to Grade 10001
AST, High, Grade 0 to Grade 10010
Total Bilirubin, High, Grade 0 to Grade 10010
Creatinine, High, Grade 0 to Grade 21000
Glucose (fasting), High, Grade 0 to Grade 20010
Glucose, Low, Grade 0 to Grade 11001
Potassium, High, Grade 0 to Grade 10001
Sodium, Low, Grade 0 to Grade 10010
Sodium, Low, Grade 1 to Grade 10011
SecondaryPart 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18

Urine samples were collected for analysis of bilirubin, glucose, leukocyte esterase, nitrite, occult blood, protein and urobilinogen by a dipstick method. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Baseline is defined as the latest pre-dose assessment with a non-missing value on or after Day -1 visit, including those from unscheduled visits. Any increase means any increase to small, moderate, severe, potentially life threatening or positive post-Baseline relative to Baseline. Data is presented for only those parameters for which participants had any increase in urinalysis results post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.

Time frame:
Baseline (Day 1) and up to Week 18
Reported as:
Count of participants · Participants
Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18
ParticipantsPart 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
Bilirubin1010
Glucose0020
Leukocyte Esterase0132
Nitrite0010
Occult Blood1124
Protein0023
Urobilinogen0001
Other pre-specifiedPart 1 and Part 2: Bioavailability of Sotrovimab IM Versus IV Formulation Using AUClast

Bioavailability of Sotrovimab was estimated using ANCOVA model with AUClast as dependent variable and ethnicity, body weight, route of administration as covariates with all available data (Part 1 \[IV\] and Part 2 \[IM\]) of Sotrovimab concentrations in serum. The AUClast Geometric Least Squares (LS) Means were estimated for each formulation and then a single parameter reported as the ratio of the AUClast geometric LS means (IM/IV) along with the 90% Confidence Interval were calculated. A single ratio parameter derived using the Geometric LS Means of AUClast IM versus IV and associated 90% Confidence Interval are presented.

Time frame:
Part 1: Day 1 (Pre-dose, at end of infusion and 1,2,6,8,24 [Day 2] and 48 [Day 3] hours after end of infusion); Weeks 2,3,4,6,8,12,18; Part 2: Day 1(Pre-dose and 1,2,6,8,24 [Day 2] and 48 [Day 3] hours after first IM injection); Weeks 2,3,4, 6,8,12,18
Reported as:
Number · Ratio
Part 1 and Part 2: Bioavailability of Sotrovimab IM Versus IV Formulation Using AUClast
RatioPart 1 and Part 2: All Participants
Part 1 and Part 2: Bioavailability of Sotrovimab IM Versus IV Formulation Using AUClast0.5179 (0.4498 to 0.5964)

Adverse events

Collected over All-cause mortality, serious adverse events (SAE) and non-serious adverse events (non-SAE) were collected up to Week 18 in Parts 1 and 2 of the study. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part 1: Placebo IV (Japanese)0/3 (0%)0/3 (0%)1/3 (33.3%)
Part 1:Placebo IV (Caucasian)0/3 (0%)0/3 (0%)1/3 (33.3%)
Part 1: Sotrovimab 500 mg IV (Japanese)0/9 (0%)0/9 (0%)2/9 (22.2%)
Part 1: Sotrovimab 500 mg IV (Caucasian)0/9 (0%)0/9 (0%)1/9 (11.1%)
Part 2: Placebo IM (Japanese)0/2 (0%)0/2 (0%)0/2 (0%)
Part 2: Placebo IM (Caucasian)0/2 (0%)0/2 (0%)1/2 (50%)
Part 2: Sotrovimab 500 mg IM (Japanese)0/10 (0%)0/10 (0%)4/10 (40%)
Part 2: Sotrovimab 500 mg IM (Caucasian)0/10 (0%)0/10 (0%)3/10 (30%)
Most frequent other events
Showing 10 of 20
Most frequent other events
EventPart 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)Part 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)
HeadacheNervous system disorders0/30/30/90/90/21/22/100/10
DiarrheaGastrointestinal disorders1/30/30/90/90/20/20/100/10
Decreased appetiteMetabolism and nutrition disorders0/31/30/90/90/20/20/100/10
Pain in extremityMusculoskeletal and connective tissue disorders0/31/30/90/90/20/20/100/10
SomnolenceNervous system disorders0/30/30/90/90/20/23/100/10
FatigueGeneral disorders0/30/30/91/90/20/20/100/10
Herpes zosterInfections and infestations0/30/31/90/90/20/20/100/10
RashSkin and subcutaneous tissue disorders0/30/31/90/90/20/20/100/10
Feeling hotGeneral disorders0/30/30/90/90/20/21/101/10
Injection site painGeneral disorders0/30/30/90/90/20/21/100/10

Baseline characteristics

Baseline characteristics were reported for the Safety Population.

Age, Customized
Age, Customized(Participants)Part 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)Part 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)Total
Participants — <=18 Years000000000
Participants — 19-64 Years339922101048
Participants — >=65 Years000000000
Sex: Female, Male
Sex: Female, Male(Participants)Part 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)Part 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)Total
Female2185217733
Male1214013315
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Part 1: Placebo IV (Japanese)Part 1:Placebo IV (Caucasian)Part 1: Sotrovimab 500 mg IV (Japanese)Part 1: Sotrovimab 500 mg IV (Caucasian)Part 2: Placebo IM (Japanese)Part 2: Placebo IM (Caucasian)Part 2: Sotrovimab 500 mg IM (Japanese)Part 2: Sotrovimab 500 mg IM (Caucasian)Total
Participants — ASIAN-JAPANESE HERITAGE30902010024
Participants — WHITE-WHITE/CAUCASIAN/EUROPEAN HERITAGE03090201024
08

Study locations

2 sites
  • Investigative Site
    Anaheim, California 92801, United States
  • Investigative Site
    Glendale, California 91206, United States
09

References and documents

Study documents

  • Study protocol · May 27, 2021
  • Statistical analysis plan · Aug 9, 2021

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 7, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04988152
Lead sponsor
Vir Biotechnology, Inc.
Collaborators
GlaxoSmithKline
Responsible party
Sponsor
First posted
Aug 3, 2021
Start date
Jul 6, 2021
Primary completion
Sep 2, 2021
Completion
Dec 7, 2021
Results posted
Jun 7, 2024
Last update
Jun 7, 2024

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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