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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Sotrovimab


Participation Criteria
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Eligibility Criteria
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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: 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).

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Participants receiving sotrovimab via Intravenous administration<br> | Biological: Sotrovimab<br>* Sotrovimab will be administered.<br>|
| Experimental: Cohort B: Participants receiving sotrovimab via Intramuscular administration<br> | Biological: Sotrovimab<br>* Sotrovimab will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight-adjusted serum clearance of sotrovimab |  | Up to Week 12 | 
| Maximum observed concentration (Cmax) following administration of sotrovimab |  | Up to Week 12 | 
| Time to reach Cmax (Tmax) following administration of sotrovimab |  | Up to Week 12 | 
| Area under the serum concentration-time curve from time zero to infinity (AUC[0-inf]) following administration of sotrovimab |  | Up to Week 12 | 
| Terminal elimination half-life (T1/2) following administration of sotrovimab |  | Up to Week 12 | 
| Apparent volume of distribution during terminal phase (Vz) following administration of sotrovimab |  | Up to Week 12 | 
| Clearance (CL) following administration of sotrovimab |  | Up to Week 12 | 
| Bioavailability (F) following administration of sotrovimab |  | Up to Week 12 | 
| Number of participants with adverse events (AEs), serious adverse events (SAEs), and AEs of special interest (AESI) |  | 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 (includes 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 require oxygen or respiratory support for premorbid conditions, disease progression is 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) |  | Baseline, at Day 5, Day 8 and Day 11 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Pharmacokinetics, Safety, Pharmacodynamics, Sotrovimab, Pediatric, Intravenous, Intramuscular