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NCT04988152

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

Completed Phase 1 Results posted Last updated 7 June 2024
What this trial tests

Phase 1 trial testing sotrovimab in Covid19 in 48 participants. Completed in 7 December 2021.

Timeline
6 July 2021
Primary endpoint
2 September 2021
7 December 2021

Quick facts

Lead sponsorVir Biotechnology, Inc.
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingsingle
Primary purposeother
Enrollment48
Start date6 July 2021
Primary completion2 September 2021
Estimated completion7 December 2021
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Vir Biotechnology, Inc. — full company profile →

Who can join

Adults 18 to 65, any sex, with Covid19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

GroupValue95% CI
Part 1: Sotrovimab 500 mg IV (Japanese)238.32± 18.5
Part 1: Sotrovimab 500 mg IV (Caucasian)188.66± 13.8
Part 1: Area Under the Serum-concentration Time Curve From Day 1 to Day 29 (AUC[D1-29]) of Sotrovimab Primary · 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.

GroupValue95% CI
Part 1: Sotrovimab 500 mg IV (Japanese)2699.29± 11.5
Part 1: Sotrovimab 500 mg IV (Caucasian)2154.90± 9.0
Part 1: Time to Cmax (Tmax) of Sotrovimab Through Day 29 Primary · 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.

GroupValue95% CI
Part 1: Sotrovimab 500 mg IV (Japanese)1.5671.55 – 6.55
Part 1: Sotrovimab 500 mg IV (Caucasian)0.7330.68 – 1.58
Part 1: Concentration at Day 29 (CD29) Following Administration of Sotrovimab Primary · 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.

GroupValue95% CI
Part 1: Sotrovimab 500 mg IV (Japanese)71.48± 15.1
Part 1: Sotrovimab 500 mg IV (Caucasian)55.56± 9.1
Part 2: Cmax of Sotrovimab Through Day 29 Primary · 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.

GroupValue95% CI
Part 2: Sotrovimab 500 mg IM (Japanese)60.33± 32.0
Part 2: Sotrovimab 500 mg IM (Caucasian)32.27± 50.4
Part 2: AUC(D1-29) of Sotrovimab Primary · 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.

GroupValue95% CI
Part 2: Sotrovimab 500 mg IM (Japanese)1378.28± 28.1
Part 2: Sotrovimab 500 mg IM (Caucasian)743.39± 46.4
Part 2: Tmax of Sotrovimab Through Day 29 Primary · 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.

GroupValue95% CI
Part 2: Sotrovimab 500 mg IM (Japanese)168.88167.8 – 334.1
Part 2: Sotrovimab 500 mg IM (Caucasian)166.60165.4 – 696.4
Part 2: CD29 of Sotrovimab Primary · 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.

GroupValue95% CI
Part 2: Sotrovimab 500 mg IM (Japanese)44.5± 30.5
Part 2: Sotrovimab 500 mg IM (Caucasian)29.14± 50.9
Part 1: Number of Participants With Serious Adverse Events (SAE) and Common Non-serious Adverse Events (Non-SAE) Through Day 29 Primary · 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 advers

SAE
GroupValue95% CI
Part 1: Placebo IV (Japanese)0
Part 1:Placebo IV (Caucasian)0
Part 1: Sotrovimab 500 mg IV (Japanese)0
Part 1: Sotrovimab 500 mg IV (Caucasian)0
Non-SAE
GroupValue95% CI
Part 1: Placebo IV (Japanese)1
Part 1:Placebo IV (Caucasian)1
Part 1: Sotrovimab 500 mg IV (Japanese)2
Part 1: Sotrovimab 500 mg IV (Caucasian)1
Part 1: Number of Participants With Adverse Events of Special Interest (AESI) Through Day 29 Primary · 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 t

IRR including hypersensitivity
GroupValue95% CI
Part 1: Placebo IV (Japanese)0
Part 1:Placebo IV (Caucasian)0
Part 1: Sotrovimab 500 mg IV (Japanese)0
Part 1: Sotrovimab 500 mg IV (Caucasian)0
Infusion Site Reactions
GroupValue95% CI
Part 1: Placebo IV (Japanese)0
Part 1:Placebo IV (Caucasian)0
Part 1: Sotrovimab 500 mg IV (Japanese)0
Part 1: Sotrovimab 500 mg IV (Caucasian)0
Part 1: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings Through Day 29 Primary · 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.

GroupValue95% CI
Part 1: Placebo IV (Japanese)0
Part 1:Placebo IV (Caucasian)0
Part 1: Sotrovimab 500 mg IV (Japanese)0
Part 1: Sotrovimab 500 mg IV (Caucasian)0
Part 1: Number of Participants With Vital Signs Grade Shifts From Baseline Grade Through Day 29 Primary · 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 Immuno

GroupValue95% CI
Part 1: Placebo IV (Japanese)0
Part 1:Placebo IV (Caucasian)0
Part 1: Sotrovimab 500 mg IV (Japanese)0
Part 1: Sotrovimab 500 mg IV (Caucasian)0

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality, serious adverse events (SAE) and non-serious adverse events (non-SAE) were collected up to Week 18 in Parts 1 and 2 of the study. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1: Placebo IV (Japanese)
Serious: 0/3 (0%)
Deaths: 0/3
Part 1:Placebo IV (Caucasian)
Serious: 0/3 (0%)
Deaths: 0/3
Part 1: Sotrovimab 500 mg IV (Japanese)
Serious: 0/9 (0%)
Deaths: 0/9
Part 1: Sotrovimab 500 mg IV (Caucasian)
Serious: 0/9 (0%)
Deaths: 0/9
Part 2: Placebo IM (Japanese)
Serious: 0/2 (0%)
Deaths: 0/2
Part 2: Placebo IM (Caucasian)
Serious: 0/2 (0%)
Deaths: 0/2
Part 2: Sotrovimab 500 mg IM (Japanese)
Serious: 0/10 (0%)
Deaths: 0/10
Part 2: Sotrovimab 500 mg IM (Caucasian)
Serious: 0/10 (0%)
Deaths: 0/10
Other adverse events (20 terms — click to expand)

ReactionSystemPart 1: Placebo IV (Japane…Part 1:Placebo IV (Caucasi…Part 1: Sotrovimab 500 mg …Part 1: Sotrovimab 500 mg …Part 2: Placebo IM (Japane…Part 2: Placebo IM (Caucas…Part 2: Sotrovimab 500 mg …Part 2: Sotrovimab 500 mg …
SomnolenceNervous system disorders
HeadacheNervous system disorders
DiarrheaGastrointestinal disorders
FatigueGeneral disorders
Feeling hotGeneral disorders
Injection site painGeneral disorders
Herpes zosterInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
Sleep paralysisNervous system disorders
Arthropod biteInjury, poisoning and procedural complications
ContusionInjury, poisoning and procedural complications
Facial bones fractureInjury, poisoning and procedural complications
Limb injuryInjury, poisoning and procedural complications
NightmarePsychiatric disorders
DysmenorrhoeaReproductive system and breast disorders
CoughRespiratory, thoracic and mediastinal disorders
Vascular painVascular disorders

Data from ClinicalTrials.gov NCT04988152 adverse events section.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Sotrovimab: First Approval.
    Heo YA. · · 2022 · cited 37× · PMID 35286623 · DOI 10.1007/s40265-022-01690-7
  2. Population pharmacokinetics and exposure-response analysis of a single dose of sotrovimab in the early treatment of patients with mild to moderate COVID-19.
    Sager JE, El-Zailik A, Passarell J, Roepcke S, et al · · 2023 · cited 10× · PMID 36922886 · DOI 10.1002/psp4.12958
  3. Severe COVID-19: Drugs and Clinical Trials.
    Ceja-Gálvez HR, Renteria-Flores FI, Nicoletti F, Hernández-Bello J, et al · · 2023 · cited 4× · PMID 37109231 · DOI 10.3390/jcm12082893
  4. Pharmacokinetics, Safety, and Tolerability of Anti-SARS-CoV-2 Monoclonal Antibody, Sotrovimab, Delivered Intravenously or Intramuscularly in Japanese and Caucasian Healthy Volunteers.
    Nader A, Alexander E, Brintziki D, Haggag AZ, et al · · 2024 · cited 3× · PMID 37955825 · DOI 10.1007/s40262-023-01319-2
  5. The immunology and immunotherapy for COVID-19.
    Liu Y, Zhou X, Liu X, Jiang X. · · 2021 · cited 3× · PMID 34915958 · DOI 10.1017/erm.2021.30
  6. Population pharmacokinetics and exposure-response analysis of sotrovimab in the early treatment of COVID-19
    Sager JE, El-Zailik A, Passarell J, Roepcke S, et al · · 2022 · DOI 10.1101/2022.11.23.22282478

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing