Covid19Phase 1NCT04988152
A Study to Investigate the PK, Safety, and Tolerability of Sotrovimab vs Placebo Administered IV or IM in Japanese and Caucasian Participants
A Phase 1 study testing sotrovimab in people with Covid19, run by Vir Biotechnology, Inc. at 2 sites in United States.
Trial summary
This is a Phase I single-dose study to investigate the pharmacokinetics, safety, and tolerability of sotrovimab vs placebo by intravenous or intramuscular administration in healthy Japanese and Caucasian participants. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Covid19
- What is being tested?
- sotrovimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Jul 2021to 7 Dec 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Investigative Site
Anaheim, California, 92801
Investigative Site
Glendale, California, 91206
About this study
Official title: A Phase I, Single-blind, Randomized, Single-dose Clinical Pharmacology Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Sotrovimab vs Placebo by Intravenous or Intramuscular Administration in Healthy Japanese and Caucasian Participants
This is a Phase I single-dose study to investigate the pharmacokinetics, safety, and tolerability of sotrovimab vs placebo by intravenous or intramuscular administration in healthy Japanese and Caucasian participants.
Read the detailed description
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of a single fixed dose of sotrovimab administered intravenously (IV) or via intramuscular (IM) injection in Japanese and Caucasian healthy volunteers. This study will occur in two parts (Part 1 and Part 2).
Part 1: Healthy Japanese and Caucasian participants will be randomized in a 4:1 ratio to receive a single IV infusion of sotrovimab or volume-matched saline placebo on Day 1. Participants will be blinded to study intervention. Safety, tolerability, immunogenicity, and PK of IV sotrovimab will be evaluated.
Part 2: Healthy Japanese and Caucasian participants will be randomized in a 4:1 ratio to receive a single IM dose of sotrovimab or volume-matched saline placebo on Day 1. Participants will be blinded to study intervention. Safety, tolerability, immunogenicity, and PK of IM sotrovimab will be evaluated.
The data from this study will be used to supplement data available from other clinical trials that were conducted in non-Japanese participants.
- Conditions
- Covid19
- Being tested
- sotrovimab, Placebo to Biologic
- Keywords
- SARS-CoV-2 coronavirus, coronavirus disease 2019, COVID-19, Japanese pharmacokinetics
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sotrovimabBiological
sotrovimab IV infusion, single dose
Placebo to BiologicOther
Sterile 0.9% (w/v) sodium chloride solution
sotrovimabBiological
Sotrovimab IM injection, single dose
Placebo to BiologicOther
Sterile 0.9% (w/v) sodium chloride solution
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Sotrovimab intravenous infusion, single dose | Experimental | Not described Receives: Biological: sotrovimab |
| Part 1 Volume-matched placebo, intravenous infusion | Placebo comparator | Not described Receives: Other: Placebo to Biologic |
| Part 2 Sotrovimab intramuscular injection, single dose | Experimental | Not described Receives: Biological: sotrovimab |
| Part 2 Volume-matched placebo, intramuscular injection | Placebo comparator | Not described Receives: Other: Placebo to Biologic |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: Up to Day 29
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.
Measured: Up to Day 29
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.
Measured: Up to Day 29
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.
Measured: Baseline (Day 1) and up to Day 29
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.
Measured: Baseline (Day 1) and up to Day 29
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.
Measured: Baseline (Day 1) and up to 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.
Measured: Part 2: Number of participants with SAE and common non-SAE through Day 29
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.
Measured: Up to Day 29
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.
Measured: Up to Day 29
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.
Measured: Baseline (Day) and up to Day 29
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.
Measured: Baseline (Day 1) and up to Day 29
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.
Measured: Baseline (Day 1) and up to Day 29
Secondary outcomes (24)
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: Weeks 2, 3, 4, 6, 8, 12 and 18
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: Weeks 2, 3, 4, 6, 8, 12 and 18
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.
Measured: Up to Week 18
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).
Measured: Up to Week 18
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.
Measured: Up to Week 18
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.
Measured: Baseline (Day 1) and up to Week 18
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.
Measured: Baseline (Day 1) and up to Week 18
Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18
Urine samples were collected for analysis of bilirubin, leukocyte esterase, occult blood and protein by a dipstick method. The dipstick test gives results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Baseline is defined as the latest pre-dose assessment with a non-missing value on or after Day -1 visit, including those from unscheduled visits. Any increase means any increase to small, moderate, severe, potentially life threatening or positive post-Baseline relative to Baseline. Data is presented for only those parameters for which participants had any increase in urinalysis results post-Baseline relative to Baseline. Number of participants with worst case any increase in urinalysis results post-Baseline relative to Baseline has been presented.
Measured: Baseline (Day 1) and up to Week 18
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.
Measured: Up to Week 18
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).
Measured: Up to Week 18
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.
Measured: Up to Week 18
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.
Measured: Baseline (Day 1) and up to Week 18
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.
Measured: Baseline (Day 1) and up to Week 18
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.
Measured: Baseline (Day 1) and up to Week 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2021
- Study start6 Jul 2021
- Primary completion2 Sep 2021
- Study completion7 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vir Biotechnology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04988152
- Sponsor's protocol ID
- VIR-7831-5009
- Other IDs
- GSK Study 217653
- Status last verified
- Sep 2022
- First submitted
- 26 Jul 2021
- Last updated
- 7 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Nader A, Alexander E, Brintziki D, Haggag AZ, Harrison SA, Hawes IA, Hezareh M, Lippa AM, Okamasa A, Okour M, Okuda N, Sager JE, Segal S, Shida Y, Skingsley A, Williams R, Yoon EY, Austin D. Pharmacokinetics, Safety, and Tolerability of Anti-SARS-CoV-2 Monoclonal Antibody, Sotrovimab, Delivered Intravenously or Intramuscularly in Japanese and Caucasian Healthy Volunteers. Clin Pharmacokinet. 2024 Jan;63(1):57-68. doi: 10.1007/s40262-023-01319-2. Epub 2023 Nov 13.
PubMed 37955825
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Single-blind, Randomized, Single-dose Clinical Pharmacology Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Sotrovimab vs Placebo by Intravenous or Intramuscular Administration in Healthy Japanese and Caucasian Participants
- ClinicalTrials.gov ID
- NCT04988152
- Acronym / sponsor ID
- VIR-7831-5009
- Conditions
- Covid19
- Keywords
- SARS-CoV-2 coronavirus, coronavirus disease 2019, COVID-19, Japanese pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Vir Biotechnology, Inc.Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- 6 Jul 2021 (actual)
- Primary completion
- 2 Sep 2021 (actual)
- Study completion
- 7 Dec 2021 (actual)
- First posted
- 3 Aug 2021 (actual)
- Results
- Posted 7 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1 Sotrovimab intravenous infusion, single dose | Experimental | Biological: sotrovimab |
| Part 1 Volume-matched placebo, intravenous infusion | Placebo comparator | Other: Placebo to Biologic |
| Part 2 Sotrovimab intramuscular injection, single dose | Experimental | Biological: sotrovimab |
| Part 2 Volume-matched placebo, intramuscular injection | Placebo comparator | Other: Placebo to Biologic |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sotrovimabsotrovimab IV infusion, single dose | Biological | Part 1 Sotrovimab intravenous infusion, single dose |
| Placebo to BiologicSterile 0.9% (w/v) sodium chloride solution | Other | Part 1 Volume-matched placebo, intravenous infusion |
| sotrovimabSotrovimab IM injection, single dose | Biological | Part 2 Sotrovimab intramuscular injection, single dose |
| Placebo to BiologicSterile 0.9% (w/v) sodium chloride solution | Other | Part 2 Volume-matched placebo, intramuscular injection |
Primary outcome
Part 1: Maximum Observed Serum Concentration (Cmax) of Sotrovimab Through Day 29
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
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
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
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
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
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
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
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
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
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
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
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
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
The Tmax was summarized using standard non-compartmental pharmacokinetic analysis methods. The median and full range are presented.
Part 2: CD29 of Sotrovimab
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
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Day 29
Time frame: 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.
24 secondary outcomes
Part 1: Cmax of Sotrovimab Through Week 18
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
Part 1: Area Under the Serum Concentration-time Curve Extrapolated to Infinite Time (AUC[0-infinity]) of Sotrovimab Through Week 18
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
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
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
Part 1: Tmax of Sotrovimab Through Week 18
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
Part 1: Time of the Last Quantifiable Concentration (Tlast) of Sotrovimab Through Week 18
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
Part 1: Terminal Elimination Half-life (t1/2) of Sotrovimab Through Week 18
Time frame: Weeks 2, 3, 4, 6, 8, 12 and 18
Part 2: Cmax of Sotrovimab Through Week 18
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
Part 2: AUC(0-infinity) of Sotrovimab Through Week 18
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
Part 2: AUClast of Sotrovimab Through Week 18
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
Part 2: Tmax of Sotrovimab Through Week 18
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
Part 2: Tlast of Sotrovimab Through Week 18
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
Part 2: T1/2 of Sotrovimab Through Week 18
Time frame: Weeks 2, 3, 4, 6, 8, 12 and 18
Part 1: Number of Participants With SAE and Common Non-SAE Through Week 18
Time frame: Up to Week 18
Part 1: Number of Participants With AESI Through Week 18
Time frame: Up to Week 18
Part 1: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18
Time frame: Up to Week 18
Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18
Time frame: Baseline (Day 1) and up to Week 18
Part 1: Number of Participants With Clinical Chemistry Shifts From Baseline Grade Through Week 18
Time frame: Baseline (Day 1) and up to Week 18
Part 1: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18
Time frame: Baseline (Day 1) and up to Week 18
Part 2: Number of Participants With SAE and Common Non-SAE Through Week 18
Time frame: Up to Week 18
Part 2: Number of Participants With AESI Through Week 18
Time frame: Up to Week 18
Part 2: Number of Participants With Abnormal Clinically Significant ECG Findings Through Week 18
Time frame: Up to Week 18
Part 2: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Week 18
Time frame: Baseline (Day 1) and up to Week 18
Part 2: Number of Participants With Clinical Chemistry Grade Shifts From Baseline Grade Through Week 18
Time frame: Baseline (Day 1) and up to Week 18
Part 2: Number of Participants With Any Increase in Worst-case Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method Through Week 18
Time frame: Baseline (Day 1) and up to Week 18
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37955825Nader A, Alexander E, Brintziki D, Haggag AZ, Harrison SA, Hawes IA, Hezareh M, Lippa AM, Okamasa A, Okour M, Okuda N, Sager JE, Segal S, Shida Y, Skingsley A, Williams R, Yoon EY, Austin D. Pharmacokinetics, Safety, and Tolerability of Anti-SARS-CoV-2 Monoclonal Antibody, Sotrovimab, Delivered Intravenously or Intramuscularly in Japanese and Caucasian Healthy Volunteers. Clin Pharmacokinet. 2024 Jan;63(1):57-68. doi: 10.1007/s40262-023-01319-2. Epub 2023 Nov 13.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sotrovimab in people with Covid19, run by Vir Biotechnology, Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Maximum Observed Serum Concentration (Cmax) of Sotrovimab Through Day 29 (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). The study lists 20 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04988152, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2024.