Pharmacokinetics, Pharmacodynamics, and Safety of Single-dose Sotrovimab in High-risk Pediatric Participants With Mild to Moderate COVID-19 (COMET-PACE)

An Open-label, Non-comparator, Multicenter Study to Describe the Pharmacokinetics (PK), Pharmacodynamics (PD; Viral Load) and Safety Following a Single Intravenous or Intramuscular Dose of Sotrovimab in Pediatric Participants With Mild to Moderate COVID-19 at High Risk of Disease Progression

This Phase 2b study will evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of sotrovimab in pediatric participants from birth to less than (<)18 years old with mild-to-moderate Coronavirus Disease-2019 (COVID-19) at high risk of disease progression.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Biological: Sotrovimab

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Cullman, Alabama, United States, 35055-1921
      • GSK Investigational Site
  • Arizona
    • Mesa, Arizona, United States, 85210
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Participant must be 32 weeks estimated gestational age (EGA), day of life (DOL) 0 to <18 years of age inclusive, at either the time of participant's signed assent (if age-appropriate) or parent(s)/legally authorized representative signing the informed consent.
• Participants with mild-moderate COVID-19.
• Participants at risk of disease progression with at least one of the following criteria: Age <1 year; Diabetes mellitus; Genetic or metabolic diseases; Obesity ); Cardiovascular disease; Sickle cell disease; Pulmonary disease; Neurologic disease; Immunosuppressed ; Baseline medical complexity (gastrostomy- or jejunostomy-dependence, parenteral nutrition dependence, tracheostomy-dependence, Baseline oxygen requirement, use of Continuous positive airway pressure [CPAP]/ Bilevel positive airway pressure [BiPAP]/ventilator support).

Exclusion Criteria

• Participant is pregnant or breastfeeding.
• Participant is currently hospitalized, or judged by the investigator as likely to require hospitalization in the next 24 hours, due to severe or critical COVID-19.
• Multisystem inflammatory syndrome in children (MIS-C).
• Prior, current, or planned future use of any of the following treatments during the study period: COVID-19 convalescent plasma, Monoclonal antibodies (mAbs) against Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (for example [e.g.], casirivimab/imdevimab), intravenous immunoglobulin (IVIG) for any indication, or dexamethasone specifically for treatment of COVID-19.
• Current use of COVID-19 treatment (authorized, approved, or investigational).

• The following exclusions related to use of an authorized or approved vaccine for SARS-CoV-2 are applicable:

  1. Receipt of any authorized or approved vaccine for SARS-CoV-2 within 48 hours prior to dosing.
  2. Planned use of any authorized or approved vaccine for SARS-CoV-2 within 90 days of study drug administration per current Centers for Disease Control and Prevention (CDC) recommendations.
• Receipt of any non-SARS-CoV-2 vaccines within 14 days (for non-live vaccines) or 28 days (for live vaccine) of screening.
• Currently enrolled in another clinical study.
• Infants <24 weeks of age: maternal receipt of IVIG, SARS-CoV-2-directed convalescent plasma or SARS-CoV-2-directed mAb(s) within 3 months prior to birth or within 5 half-lives of the investigational product (whichever is longer).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Sotrovimab Intravenous (IV) (6 to less than [<] 12 years); Participants in the age group 6 to < 12 years received up to a maximum of 500 milligram (mg) sotrovimab based on the body weight through Intravenous administration on Day 1	Biological: Sotrovimab; Sotrovimab will be administered.
Experimental: Cohort A: Sotrovimab Intravenous (IV) (12 to less than [<] 18 years); Participants in the age group 12 to < 18 years received up to a maximum of 500 milligram (mg) sotrovimab based on the body weight through Intravenous administration on Day 1	Biological: Sotrovimab; Sotrovimab will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Weight-Adjusted Serum Clearance (CL) of Sotrovimab	Blood samples were collected at indicated timepoints and Pharmacokinetic (PK) analysis was performed. PK parameters were determined by population PK modelling method. The model considered the body weight of each participant to calculate the serum clearance of sotrovimab.	Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
Maximum Observed Concentration (Cmax) Following Administration of Sotrovimab	Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods using Phoenix WinNonlin. The log-transformed data is transformed back to the original scale and presented here.	Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
Time to Reach Cmax (Tmax) Following Administration of Sotrovimab	Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.	Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0-inf]) Following Administration of Sotrovimab	Blood samples were collected at indicated timepoints and Pharmacokinetic (PK) analysis was performed. PK parameters were determined by population PK modelling method.	Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
Terminal Elimination Half-Life (T1/2) Following Administration of Sotrovimab	Blood samples were collected at indicated timepoints and Pharmacokinetic (PK) analysis was performed. PK parameters were determined by population PK modelling method.	Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
Apparent Volume of Distribution During Terminal Phase (Vz) Following Administration of Sotrovimab	Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The log-transformed data is transformed back to the original scale and presented here.	Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
Clearance (CL) Following Administration of Sotrovimab	Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The log-transformed data is transformed back to the original scale and presented here.	Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
Relative Bioavailability (F) Following Administration of Sotrovimab	Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.	Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESI)	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. A SAE is any untoward medical occurrence that, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity and/or can result in death. Protocol defined AESIs were included.	Up to Day 29
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESI) Up to Week 36	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is any untoward medical occurrence that, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity and/or can result in death. Protocol defined AESIs were included.	Up to Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Progression of COVID-19 Through Day 29	Progression of COVID-19 is defined as need for attended medical visit (including the visit to a hospital emergency room for management of illness or hospitalization for acute management of illness) or escalation to higher level of medical care or death.	Up to Day 29
Number of Participants With Development of Severe and/or Critical Respiratory COVID-19 Through Day 29	Severe and/or critical respiratory COVID-19 as manifested by requirement for supplemental oxygen through Day 29. For participants who required oxygen or respiratory support for premorbid conditions, disease progression was defined as any sustained (greater than [>]24 hours) increase in the level or method of oxygen support required.	Up to Day 29
Change From Baseline in Viral Load in Nasal Secretions Measured by Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR)	The viral load change from baseline in nasal secretions was measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) at Day 5, Day 8, and Day 11.	Baseline (Day 1), at Day 5, Day 8 and Day 11

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: Vir Biotechnology, Inc.
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Actual): June 14, 2023
• Study Completion (Actual): June 14, 2023

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: November 16, 2021
• First Posted (Actual): November 17, 2021

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Pediatric; Pharmacokinetics; COVID-19; Intravenous; Pharmacodynamics; Sotrovimab; Intramuscular
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Infective Agents; Antiviral Agents; Sotrovimab
• Other Study ID Numbers: 215226

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No