Covid19
Conditions
Keywords
SARS-CoV-2 coronavirus, coronavirus disease 2019, COVID-19, Japanese pharmacokinetics
Brief 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.
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.
Interventions
BIOLOGICALsotrovimab
sotrovimab IV infusion, single dose
OTHERPlacebo to Biologic
Sterile 0.9% (w/v) sodium chloride solution
Sponsors
GlaxoSmithKline
Vir Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Baseline (Day 1) and up to 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. |
| Part 1: Maximum Observed Serum Concentration (Cmax) of Sotrovimab Through Day 29 | 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 | 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. |
| Part 1: Area Under the Serum-concentration Time Curve From Day 1 to Day 29 (AUC[D1-29]) of Sotrovimab | 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 | 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. |
| Part 1: Time to Cmax (Tmax) of Sotrovimab Through Day 29 | 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 | The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented. |
| Part 1: Concentration at Day 29 (CD29) Following Administration of Sotrovimab | 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 | The CD29 was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. |
| Part 2: Cmax of Sotrovimab Through Day 29 | 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 | 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. |
| Part 2: AUC(D1-29) of Sotrovimab | 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 | 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. |
| Part 2: Tmax of Sotrovimab Through Day 29 | 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 | The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented. |
| Part 2: CD29 of Sotrovimab | 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 | The CD29 was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. |
| Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29 | Up to 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. |
| Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 | Up to 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. |
| Part 1: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings Through Day 29 | Up to 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. |
| Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | Baseline (Day 1) and up to 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. |
| Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Baseline (Day 1) and up to 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. |
| Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Baseline (Day 1) and up to 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. |
| Part 2: Number of Participants With SAE and Common Non-SAE Through Day 29 | 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. |
| Part 2: Number of Participants With AESI Through Day 29 | Up to 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. |
| Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Day 29 | Up to 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. |
| Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | Baseline (Day) and up to 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. |
| Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Baseline (Day 1) and up to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Number of Participants With AESI Through Week 18 | Up to 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). |
| Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18 | Up to 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. |
| Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Baseline (Day 1) and up to 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. |
| Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Baseline (Day 1) and up to 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. |
| Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | Baseline (Day 1) and up to 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. |
| Part 1: Cmax of Sotrovimab Through Week 18 | 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 | 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. |
| Part 1: Area Under the Serum Concentration-time Curve Extrapolated to Infinite Time (AUC[0-infinity]) of Sotrovimab Through Week 18 | 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 | The AUC(0-infinity) was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. |
| 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 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 | 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. |
| Part 1: Tmax of Sotrovimab Through Week 18 | 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 | The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented. |
| Part 1: Time of the Last Quantifiable Concentration (Tlast) of Sotrovimab Through Week 18 | 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 | The Tlast was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented. |
| Part 1: Terminal Elimination Half-life (t1/2) of Sotrovimab Through Week 18 | Weeks 2, 3, 4, 6, 8, 12 and 18 | The T1/2 was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented. |
| Part 2: Cmax of Sotrovimab Through Week 18 | 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 | 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. |
| Part 2: AUC(0-infinity) of Sotrovimab Through Week 18 | 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 | The AUC0-infinity was summarized using standard non-compartmental pharmacokinetic analysis methods. The geometric mean and geometric coefficient of variation are presented. |
| Part 2: AUClast of Sotrovimab Through Week 18 | 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 | 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. |
| Part 2: Tmax of Sotrovimab Through Week 18 | 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 | The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented. |
| Part 2: Tlast of Sotrovimab Through Week 18 | 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 | The Tlast was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented. |
| Part 2: T1/2 of Sotrovimab Through Week 18 | Weeks 2, 3, 4, 6, 8, 12 and 18 | The T1/2 was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented. |
| Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18 | Up to 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. |
| Part 1: Number of Participants With AESI Through Week 18 | Up to 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). |
| Part 1: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18 | Up to 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. |
| Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | Baseline (Day 1) and up to 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. |
| Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Baseline (Day 1) and up to 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. |
| Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Baseline (Day 1) and up to 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. |
| Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18 | Up to 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and Part 2: Bioavailability of Sotrovimab IM Versus IV Formulation Using AUClast | 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 | 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. |
Countries
United States
Participant flow
Recruitment details
This study was conducted in the United States.
Pre-assignment details
A total of 48 participants (24 participants in Part 1 and 24 participants in Part 2) were enrolled in the study (Safety Population comprised of all randomized participants who were exposed to study intervention).
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Placebo IV (Japanese) Japanese participants received a volume-matched saline placebo (Sterile 0.9 percent \[%\] weight/volume \[w/v\] sodium chloride solution) matching intravenous (IV) infusion of sotrovimab on Day 1. | 3 |
| Part 1:Placebo IV (Caucasian) Caucasian participants received a volume-matched saline placebo (Sterile 0.9% \[w/v\] sodium chloride solution) matching IV infusion of sotrovimab on Day 1 | 3 |
| Part 1: Sotrovimab 500 mg IV (Japanese) Japanese participants received a single 500 milligrams (mg) IV infusion of sotrovimab on Day 1 | 9 |
| Part 1: Sotrovimab 500 mg IV (Caucasian) Caucasian participants received a single 500 mg IV infusion of sotrovimab on Day 1 | 9 |
| Part 2: Placebo IM (Japanese) Japanese participants received a volume-matched saline placebo (Sterile 0.9% \[w/v\] sodium chloride solution) matching intramuscular (IM) injection of sotrovimab on Day 1. | 2 |
| Part 2: Placebo IM (Caucasian) Caucasian participants received a volume-matched saline placebo (Sterile 0.9% \[w/v\] sodium chloride solution) matching IM injection of sotrovimab on Day 1. | 2 |
| Part 2: Sotrovimab 500 mg IM (Japanese) Japanese participants received a single 500 mg IM injection of sotrovimab (administered as two 4 milliliters \[mL\] injections, one in each dorsogluteal muscle) on Day 1. | 10 |
| Part 2: Sotrovimab 500 mg IM (Caucasian) Caucasian participants received a single 500 mg IM injection of sotrovimab (administered as two 4 mL injections, one in each dorsogluteal muscle) on Day 1. | 10 |
| Total | 48 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized Participants <=18 Years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Participants 19-64 Years | 3 Participants | 3 Participants | 9 Participants | 9 Participants | 2 Participants | 2 Participants | 10 Participants | 10 Participants | 48 Participants |
| Age, Customized Participants >=65 Years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Participants ASIAN-JAPANESE HERITAGE | 3 Participants | 0 Participants | 9 Participants | 0 Participants | 2 Participants | 0 Participants | 10 Participants | 0 Participants | 24 Participants |
| Race/Ethnicity, Customized Participants WHITE-WHITE/CAUCASIAN/EUROPEAN HERITAGE | 0 Participants | 3 Participants | 0 Participants | 9 Participants | 0 Participants | 2 Participants | 0 Participants | 10 Participants | 24 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 8 Participants | 5 Participants | 2 Participants | 1 Participants | 7 Participants | 7 Participants | 33 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 4 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 9 | 0 / 9 | 0 / 2 | 0 / 2 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 1 / 3 | 1 / 3 | 2 / 9 | 1 / 9 | 0 / 2 | 1 / 2 | 4 / 10 | 3 / 10 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 9 | 0 / 9 | 0 / 2 | 0 / 2 | 0 / 10 | 0 / 10 |
Outcome results
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Area Under the Serum-concentration Time Curve From Day 1 to Day 29 (AUC[D1-29]) of Sotrovimab | 2699.29 Day*micrograms per milliliter | Geometric Coefficient of Variation 11.5 |
| 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 Sotrovimab | 2154.90 Day*micrograms per milliliter | Geometric Coefficient of Variation 9 |
90% CI: [0.9281, 1.1908]
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Concentration at Day 29 (CD29) Following Administration of Sotrovimab | 71.48 Micrograms per milliliter | Geometric Coefficient of Variation 15.1 |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Concentration at Day 29 (CD29) Following Administration of Sotrovimab | 55.56 Micrograms per milliliter | Geometric Coefficient of Variation 9.1 |
Primary
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
Population: Pharmacokinetic Population comprised all participants in the Safety Population (All randomized participants who were exposed to study intervention) who had at least 1 non-missing PK assessment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Maximum Observed Serum Concentration (Cmax) of Sotrovimab Through Day 29 | 238.32 Micrograms per milliliter | Geometric Coefficient of Variation 18.5 |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Maximum Observed Serum Concentration (Cmax) of Sotrovimab Through Day 29 | 188.66 Micrograms per milliliter | Geometric Coefficient of Variation 13.8 |
90% CI: [0.8519, 1.35]
Primary
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
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings Through Day 29 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings Through Day 29 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings Through Day 29 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings Through Day 29 | 0 Participants |
Primary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 | Infusion Site Reactions | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 | IRR including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 | IRR including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 | Infusion Site Reactions | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 | Infusion Site Reactions | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 | IRR including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 | Infusion Site Reactions | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 | IRR including hypersensitivity | 0 Participants |
Primary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Bilirubin | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Leukocyte Esterase | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Occult Blood | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Protein | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Leukocyte Esterase | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Occult Blood | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Protein | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Bilirubin | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Occult Blood | 3 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Leukocyte Esterase | 2 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Protein | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Bilirubin | 2 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Protein | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Leukocyte Esterase | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Bilirubin | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Occult Blood | 2 Participants |
Primary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose (fasting), High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose, Low, Grade 1 to Grade 0 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Total Bilirubin, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose (fasting), High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Direct Bilirubin, High, Grade 0 to Grade 3 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose (fasting), High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Direct Bilirubin, High, Grade 0 to Grade 3 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose, Low, Grade 1 to Grade 0 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Total Bilirubin, High, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose (fasting), High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Direct Bilirubin, High, Grade 0 to Grade 3 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose, Low, Grade 1 to Grade 0 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose (fasting), High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose (fasting), High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Total Bilirubin, High, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose, Low, Grade 1 to Grade 0 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Total Bilirubin, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Direct Bilirubin, High, Grade 0 to Grade 3 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose (fasting), High, Grade 0 to Grade 1 | 2 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose (fasting), High, Grade 0 to Grade 2 | 1 Participants |
Primary
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
Population: Safety Population comprised of all randomized participants who were exposed to study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29 | Non-SAE | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29 | Non-SAE | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29 | Non-SAE | 2 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29 | Non-SAE | 1 Participants |
Primary
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
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | 0 Participants |
Primary
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
Population: Pharmacokinetic Population. Only those participants with data available at specified time point were analyzed. Participants with slow drug distribution following IV infusion were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Time to Cmax (Tmax) of Sotrovimab Through Day 29 | 1.567 Hours |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Time to Cmax (Tmax) of Sotrovimab Through Day 29 | 0.733 Hours |
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: AUC(D1-29) of Sotrovimab | 1378.28 Day*micrograms per milliliter | Geometric Coefficient of Variation 28.1 |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: AUC(D1-29) of Sotrovimab | 743.39 Day*micrograms per milliliter | Geometric Coefficient of Variation 46.4 |
90% CI: [1.1236, 2.2413]
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: CD29 of Sotrovimab | 44.5 Micrograms per milliliter | Geometric Coefficient of Variation 30.5 |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: CD29 of Sotrovimab | 29.14 Micrograms per milliliter | Geometric Coefficient of Variation 50.9 |
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Cmax of Sotrovimab Through Day 29 | 60.33 Micrograms per milliliter | Geometric Coefficient of Variation 32 |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Cmax of Sotrovimab Through Day 29 | 32.27 Micrograms per milliliter | Geometric Coefficient of Variation 50.4 |
90% CI: [1.15, 2.5129]
Primary
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
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Day 29 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Day 29 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Day 29 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Day 29 | 0 Participants |
Primary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Day 29 | Injection-related reactions including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Day 29 | Injection Site Reaction | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Day 29 | Injection Site Reaction | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Day 29 | Injection-related reactions including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Day 29 | Injection-related reactions including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Day 29 | Injection Site Reaction | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Day 29 | Injection-related reactions including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Day 29 | Injection Site Reaction | 0 Participants |
Primary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Occult Blood | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Glucose | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Protein | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Leukocyte Esterase | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Bilirubin | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Leukocyte Esterase | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Occult Blood | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Protein | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Glucose | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Bilirubin | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Leukocyte Esterase | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Bilirubin | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Glucose | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Occult Blood | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Protein | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Occult Blood | 4 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Glucose | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Bilirubin | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Leukocyte Esterase | 2 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29 | Protein | 2 Participants |
Primary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Potassium, High, Grade 0 to Grade 4 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Total Bilirubin, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose, Low, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | ALP, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Sodium, Low, Grade 1 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose, Low, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Total Bilirubin, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | ALP, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Potassium, High, Grade 0 to Grade 4 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Sodium, Low, Grade 1 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose, Low, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | ALP, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Sodium, Low, Grade 1 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Potassium, High, Grade 0 to Grade 4 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Total Bilirubin, High, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Potassium, High, Grade 0 to Grade 4 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Glucose, Low, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | ALP, High, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Sodium, Low, Grade 1 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Day 29 | Total Bilirubin, High, Grade 0 to Grade 1 | 0 Participants |
Primary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With SAE and Common Non-SAE Through Day 29 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With SAE and Common Non-SAE Through Day 29 | Non-SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With SAE and Common Non-SAE Through Day 29 | Non-SAE | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With SAE and Common Non-SAE Through Day 29 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With SAE and Common Non-SAE Through Day 29 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With SAE and Common Non-SAE Through Day 29 | Non-SAE | 4 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With SAE and Common Non-SAE Through Day 29 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With SAE and Common Non-SAE Through Day 29 | Non-SAE | 2 Participants |
Primary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | Pulse rate; Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | DBP; Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | SBP; Grade 1 to Grade 0 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | SBP; Grade 1 to Grade 0 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | DBP; Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | Pulse rate; Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | SBP; Grade 1 to Grade 0 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | DBP; Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | Pulse rate; Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | DBP; Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | Pulse rate; Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 | SBP; Grade 1 to Grade 0 | 0 Participants |
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Tmax of Sotrovimab Through Day 29 | 168.88 Hours |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Tmax of Sotrovimab Through Day 29 | 166.60 Hours |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | 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 | 6597.35 Day*micrograms per milliliter | Geometric Coefficient of Variation 10.9 |
| 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 18 | 5098.64 Day*micrograms per milliliter | Geometric Coefficient of Variation 12 |
90% CI: [0.9286, 1.2268]
Secondary
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
Population: Pharmacokinetic Population. Only those participants with data available at specified time points were analyzed. Participants with the extrapolated portion of AUCinfinity (% AUCex) \>20% were excluded.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Area Under the Serum Concentration-time Curve Extrapolated to Infinite Time (AUC[0-infinity]) of Sotrovimab Through Week 18 | 7513.23 Day*micrograms per milliliter | Geometric Coefficient of Variation 22.1 |
| 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 18 | 5388.17 Day*micrograms per milliliter | Geometric Coefficient of Variation 30.8 |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Cmax of Sotrovimab Through Week 18 | 238.32 Micrograms per milliliter | Geometric Coefficient of Variation 18.5 |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Cmax of Sotrovimab Through Week 18 | 188.66 Micrograms per milliliter | Geometric Coefficient of Variation 13.8 |
90% CI: [0.8519, 1.35]
Secondary
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
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18 | 0 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With AESI Through Week 18 | IRR including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With AESI Through Week 18 | Hypersensitivity (SMQ narrow) | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With AESI Through Week 18 | Infusion Site Reaction | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With AESI Through Week 18 | Immunogenicity related ADR | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With AESI Through Week 18 | AE potentially related to ADE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With AESI Through Week 18 | AE potentially related to ADE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With AESI Through Week 18 | Infusion Site Reaction | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With AESI Through Week 18 | Hypersensitivity (SMQ narrow) | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With AESI Through Week 18 | Immunogenicity related ADR | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With AESI Through Week 18 | IRR including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With AESI Through Week 18 | IRR including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With AESI Through Week 18 | Immunogenicity related ADR | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With AESI Through Week 18 | Hypersensitivity (SMQ narrow) | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With AESI Through Week 18 | Infusion Site Reaction | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With AESI Through Week 18 | AE potentially related to ADE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With AESI Through Week 18 | Infusion Site Reaction | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With AESI Through Week 18 | Immunogenicity related ADR | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With AESI Through Week 18 | IRR including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With AESI Through Week 18 | Hypersensitivity (SMQ narrow) | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With AESI Through Week 18 | AE potentially related to ADE | 0 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Occult Blood | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Protein | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Bilirubin | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Leukocyte Esterase | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Leukocyte Esterase | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Protein | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Occult Blood | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Bilirubin | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Protein | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Bilirubin | 2 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Leukocyte Esterase | 3 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Occult Blood | 4 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Occult Blood | 3 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Leukocyte Esterase | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Protein | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Bilirubin | 0 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | AST, High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Glucose (fasting), High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Total Bilirubin, High, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Glucose (fasting), High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Glucose, Low, Grade 1 to Grade 0 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Total Bilirubin, High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Sodium, Low, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Direct Bilirubin, High, Grade 0 to Grade 3 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Glucose, Low, Grade 1 to Grade 0 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Total Bilirubin, High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Glucose (fasting), High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Total Bilirubin, High, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | AST, High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Direct Bilirubin, High, Grade 0 to Grade 3 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Glucose (fasting), High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Sodium, Low, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Total Bilirubin, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Glucose, Low, Grade 1 to Grade 0 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Sodium, Low, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Total Bilirubin, High, Grade 0 to Grade 2 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | AST, High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Glucose (fasting), High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Direct Bilirubin, High, Grade 0 to Grade 3 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Glucose (fasting), High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Sodium, Low, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | AST, High, Grade 0 to Grade 2 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Total Bilirubin, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Total Bilirubin, High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Direct Bilirubin, High, Grade 0 to Grade 3 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Glucose (fasting), High, Grade 0 to Grade 1 | 3 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Glucose (fasting), High, Grade 0 to Grade 2 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18 | Glucose, Low, Grade 1 to Grade 0 | 0 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18 | Non-SAE | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18 | Non-SAE | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18 | Non-SAE | 2 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18 | Non-SAE | 1 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | 0 Participants |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Terminal Elimination Half-life (t1/2) of Sotrovimab Through Week 18 | 56.38 Day |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Terminal Elimination Half-life (t1/2) of Sotrovimab Through Week 18 | 58.85 Day |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Time of the Last Quantifiable Concentration (Tlast) of Sotrovimab Through Week 18 | 125.98 Day |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Time of the Last Quantifiable Concentration (Tlast) of Sotrovimab Through Week 18 | 125.98 Day |
Secondary
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
Population: Pharmacokinetic Population. Only those participants with data available at specified time points were analyzed. Participants with slow drug distribution following IV infusion were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1: Tmax of Sotrovimab Through Week 18 | 0.065 Day |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 1: Tmax of Sotrovimab Through Week 18 | 0.031 Day |
Secondary
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
Population: Pharmacokinetic Population. Only those participants with data available at specified time points were analyzed. Participants with the extrapolated portion of AUCinfinity (% AUCex) \>20% were excluded.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: AUC(0-infinity) of Sotrovimab Through Week 18 | 5687.48 Day*micrograms per milliliter | — |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: AUC(0-infinity) of Sotrovimab Through Week 18 | 2788.57 Day*micrograms per milliliter | Geometric Coefficient of Variation 60.9 |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: AUClast of Sotrovimab Through Week 18 | 4018.36 Day*micrograms per milliliter | Geometric Coefficient of Variation 25.1 |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: AUClast of Sotrovimab Through Week 18 | 2148.93 Day*micrograms per milliliter | Geometric Coefficient of Variation 39.6 |
90% CI: [1.1777, 2.1106]
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Cmax of Sotrovimab Through Week 18 | 60.33 Micrograms per milliliter | Geometric Coefficient of Variation 32 |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Cmax of Sotrovimab Through Week 18 | 32.27 Micrograms per milliliter | Geometric Coefficient of Variation 50.4 |
90% CI: [1.15, 2.5129]
Secondary
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
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18 | 0 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Week 18 | Immunogenicity related ADR | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Week 18 | Injection Site Reaction | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Week 18 | Hypersensitivity (SMQ narrow) | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Week 18 | Injection related reaction including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Week 18 | AE potentially related to ADE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Week 18 | Immunogenicity related ADR | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Week 18 | AE potentially related to ADE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Week 18 | Injection related reaction including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Week 18 | Hypersensitivity (SMQ narrow) | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Week 18 | Injection Site Reaction | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Week 18 | Immunogenicity related ADR | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Week 18 | Injection Site Reaction | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Week 18 | AE potentially related to ADE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Week 18 | Injection related reaction including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With AESI Through Week 18 | Hypersensitivity (SMQ narrow) | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Week 18 | AE potentially related to ADE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Week 18 | Injection related reaction including hypersensitivity | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Week 18 | Injection Site Reaction | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Week 18 | Immunogenicity related ADR | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With AESI Through Week 18 | Hypersensitivity (SMQ narrow) | 0 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Glucose | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Protein | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Occult Blood | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Leukocyte Esterase | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Bilirubin | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Urobilinogen | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Nitrite | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Glucose | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Leukocyte Esterase | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Nitrite | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Occult Blood | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Protein | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Urobilinogen | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Bilirubin | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Nitrite | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Protein | 2 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Glucose | 2 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Urobilinogen | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Leukocyte Esterase | 3 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Bilirubin | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Occult Blood | 2 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Bilirubin | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Glucose | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Protein | 3 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Leukocyte Esterase | 2 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Occult Blood | 4 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Nitrite | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18 | Urobilinogen | 1 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | ALT, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Creatinine, High, Grade 0 to Grade 2 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Total Bilirubin, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Glucose (fasting), High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | ALP, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Sodium, Low, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Glucose, Low, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | AST, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Sodium, Low, Grade 1 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Potassium, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Sodium, Low, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Total Bilirubin, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Potassium, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Creatinine, High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Sodium, Low, Grade 1 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | ALT, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | ALP, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Glucose, Low, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | AST, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Glucose (fasting), High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Sodium, Low, Grade 1 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Potassium, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Sodium, Low, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | ALT, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | ALP, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | AST, High, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Total Bilirubin, High, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Creatinine, High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Glucose (fasting), High, Grade 0 to Grade 2 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Glucose, Low, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | AST, High, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Sodium, Low, Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Glucose (fasting), High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | ALP, High, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | ALT, High, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Potassium, High, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Glucose, Low, Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Sodium, Low, Grade 1 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Creatinine, High, Grade 0 to Grade 2 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18 | Total Bilirubin, High, Grade 0 to Grade 1 | 0 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18 | Non-SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18 | Non-SAE | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18 | Non-SAE | 4 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18 | SAE | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18 | Non-SAE | 3 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18 | SAE | 0 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | SBP; Grade 1 to Grade 0 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | DBP; Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | DBP; Grade 0 to Grade 1 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | SBP; Grade 1 to Grade 0 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | DBP; Grade 0 to Grade 1 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | SBP; Grade 1 to Grade 0 | 1 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | SBP; Grade 1 to Grade 0 | 0 Participants |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18 | DBP; Grade 0 to Grade 1 | 0 Participants |
Secondary
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
Population: Pharmacokinetic Population. Only those participants with data available at specified time points were analyzed. Participants with adjusted regression coefficient for the slope of elimination phase (R\^2) \<0.8 were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: T1/2 of Sotrovimab Through Week 18 | 67.28 Day |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: T1/2 of Sotrovimab Through Week 18 | 67.40 Day |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Tlast of Sotrovimab Through Week 18 | 127.54 Day |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Tlast of Sotrovimab Through Week 18 | 125.52 Day |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 2: Tmax of Sotrovimab Through Week 18 | 7.04 Day |
| Part 1: Sotrovimab 500 mg IV (Caucasian) | Part 2: Tmax of Sotrovimab Through Week 18 | 6.94 Day |
Other Pre-specified
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
Population: Pharmacokinetic Population. Given that bioavailability assessment requires comparison of exposures between IM and IV routes of administration, data from Part 1 (IV) and Part 2 (IM) were combined to enable an estimation of bioavailability of IM formulation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Sotrovimab 500 mg IV (Japanese) | Part 1 and Part 2: Bioavailability of Sotrovimab IM Versus IV Formulation Using AUClast | 0.5179 Ratio |