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

NCT05124210 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 215226
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

COVID-19

Keywords

COVID-19; Pharmacokinetics; Safety; Pharmacodynamics; Sotrovimab; Pediatric; Intravenous; Intramuscular

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (3)

• Number of Participants With Progression of COVID-19 Through Day 29

  Up to Day 29

• Number of Participants With Development of Severe and/or Critical Respiratory COVID-19 Through Day 29

  Up to Day 29

• Change From Baseline in Viral Load in Nasal Secretions Measured by Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR)

  Baseline (Day 1), at Day 5, Day 8 and Day 11

Study Arms (2)

Cohort A: Sotrovimab Intravenous (IV) (6 to less than [<] 12 years)

EXPERIMENTAL

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

Cohort A: Sotrovimab Intravenous (IV) (12 to less than [<] 18 years)

EXPERIMENTAL

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

Interventions

Sotrovimab BIOLOGICAL

Sotrovimab will be administered.

Cohort A: Sotrovimab Intravenous (IV) (12 to less than [<] 18 years); Cohort A: Sotrovimab Intravenous (IV) (6 to less than [<] 12 years)

Eligibility Criteria

• Age: 0 Days - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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).
• Receipt of any authorized or approved vaccine for SARS-CoV-2 within 48 hours prior to dosing.
• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Vir Biotechnology, Inc.: collaborator

Study Sites (2)

GSK Investigational Site

Cullman, Alabama, 35055-1921, United States

Location

GSK Investigational Site

Mesa, Arizona, 85210, United States

Location

MeSH Terms

Conditions

COVID-19

Interventions

sotrovimab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: November 17, 2021
• Study Start: December 16, 2021
• Primary Completion: June 14, 2023
• Study Completion: June 14, 2023
• Last Updated: January 3, 2024
• Results First Posted: January 3, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

US (2)