Pharmacokinetics, pharmacodynamics, and safety of single-dose sotrovimab in high-risk pediatric participants with mild to moderate COVID-19

Phase 1

Active, not recruiting

• Conditions: COVID-19 at high risk of disease progression; MedDRA version: 20.0Level: SOCClassification code 10021881Term: Infections and infestationsSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 23.0Level: PTClassification code 10084268Term: COVID-19System Organ Class: 10021881 - Infections and infestations; MedDRA version: 23.1Level: LLTClassification code 10084401Term: COVID-19 respiratory infectionSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2021-003717-18-GR
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-11-10
• Last Update Posted: 18 July 2023

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

Age
1.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.

Type of Participant and Disease Characteristics
2. Participants with mild-moderate COVID-19, as defined by:
• A positive SARS-CoV-2 test result by any validated qRT-PCR or other nucleic acid amplification test (NAAT) AND
• SpO2 =94% on room air AND
• Have one or more of the following symptoms: fever, chills, cough, sore throat, malaise, headache, joint or muscle pain, change in smell or taste, vomiting, diarrhea, shortness of breath, poor appetite or poor feeding, nasal congestion/runny nose, lethargy AND
• Less than or equal to 7 days from onset of symptoms to dosing day (Day 1).

3. Participants at risk of disease progression with at least one of the following criteria:
• Age <1 year
• Diabetes mellitus
• Genetic or metabolic diseases
• Obesity (as defined as body mass index (kg/m2) =95th percentile for age and sex based on local growth charts for children =2 years of age)
• Cardiovascular disease
• Sickle cell disease
• Pulmonary disease
• Neurologic disease
• Immunosuppressed (due to certain medical conditions or being on medications that weaken the immune system
o Use of systemic corticosteroids is included as defined by dose =0.5 mg/kg/day or 20 mg/day prednisone equivalents (whichever dose is the lower of the two) taken for =2 weeks
• Baseline medical complexity (gastrostomy- or jejunostomy-dependence, parenteral nutrition dependence, tracheostomy-dependence, baseline oxygen requirement, use of CPAP/BiPAP/ventilator support).

Weight
4. Body weight with the range stated below:
• Preterm newborn infants and term newborn infants: =2 kg
• Children 2 years to <18 years:
o Body mass index (BMI) =5th percentile for age based on local growth charts.

Sex and Contraceptive/Barrier Requirements
5. Male and/or female
• Contraception and barriers as well as pregnancy testing is required for females only, as appropriate for the age and sexual activity of pediatric participants and as required by local regulations regarding the methods of contraception for those participating in clinical studies.
• A female participant is eligible to participate if she is not breastfeeding and is either:
• Premenarcheal or
• Not pregnant as confirmed by a negative pregnancy test (serum or highly sensitive urine as required by local regulations) at Screening, before the first dose of study intervention, if of reproductive potential.
o If a urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
o See protocol for additional requirements for pregnancy testing during the study participation.
Women of childbearing potential (WOCBP) must commit to using a contraceptive method that is highly effective, with a failure rate of <1%, during the study intervention period and for at least 36 weeks after the last dose of study intervention. The investigator should evaluate potential for contraceptive method failure in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a female with an early undetected pregnancy.
6. The inve

Exclusion Criteria

Medical Conditions
1. Pregnant or breastfeeding.
2. Currently hospitalized, or judged by the investigator as likely to require hospitalization in the next 24 hours, due to severe or critical COVID-19.
Note: If the infant has been hospitalized due to other reasons (e.g., prematurity) or will be hospitalized for reason of administering the study treatment then they can be included in the study.
3. Respiratory rate:
• 0-6 months: >60 breaths/minute (min)
• 6 months to 5 years: >30 breaths/min
• 6 years to <18 years: >20 breaths/min
4. Shortness of breath at rest or respiratory distress.
5. Shock (septic, neurogenic, anaphylactic, cardiogenic, or hypovolemic shock; systemic inflammatory response syndrome).
6. Multiorgan dysfunction.
7. Participants who, in the judgement of the investigator are likely to die in the next 7 days.
8. Multisystem inflammatory syndrome in children (MIS-C) [CDC HAN, 2020], defined as a participant:
a. Participants presenting with fever =38°C, laboratory evidence of inflammation (such as elevated C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid, lactate dehydrogenase [LDH], interleukin 6 [IL-6], neutrophilia, lymphopenia or hypoalbuminemia) and evidence of clinically severe illness requiring hospitalization, with multisystem (=2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological);
AND
b. No alternative plausible diagnoses;
AND
c. Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within the 4 weeks prior to the onset of symptoms.
9. Post-conceptional age less than 32 completed weeks at time of Screening.
10. History of sudden infant death or unexplained death in a sibling.
11. For Cohort B only: Participant has any condition that would prohibit receipt of IM injections in the investigator’s opinion such as coagulation disorder, bleeding diathesis, or thrombocytopenia (platelet count <50,000/mm3).

Prior/Concomitant Therapy
12. Prior, current, or planned future use of any of the following treatments during the study period: COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (e.g., casirivimab/imdevimab), intravenous immunoglobulin (IVIG) for any indication, or dexamethasone specifically for treatment of COVID-19.
13. Current use of COVID-19 treatment (authorized, approved, or investigational).
14. The following exclusions related to use of an authorized or approved vaccine for SARS-CoV-2 are applicable:
a) Receipt of any authorized or approved vaccine for SARS-CoV-2 within 48 hours prior to dosing.
b) Planned use of any authorized or approved vaccine for SARS-CoV-2 within 90 days of study drug administration per current CDC recommendations.
15. Receipt of any non-SARS-CoV-2 vaccines within 14 days (for non-live vaccines) or 28 days (for live vaccine) of Screening.

Prior/Concurrent Clinical Study Experience
16. Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, mAbs against SARS-CoV-2 (e.g. casirivimab/imdevimab) or IVIG within 3 months or within 5 half-lives of the investigational product (whichever is longer) prior to the Screening visit.
17. Has participated, is participating, or plans to participate during the study period in a clinical research study evaluation of any authorized, approved or investigational vaccine for SARS

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the pharmacokinetics by IV or IM administration of sotrovimab in children from birth to <18 years<br><br>To evaluate the safety and tolerability of sotrovimab by IV or IM administration;Secondary Objective: To evaluate disease progression following IV or IM administration of sotrovimab.<br><br>To characterize the effect of IV or IM administration of sotrovimab on SARS-CoV-2 viral load in respiratory tract samples among participants infected with SARS-CoV-2;Primary end point(s): Body weight-adjusted serum clearance of sotrovimab<br><br>Serum PK of sotrovimab administered by IM injection or IV infusion (PK parameters may include Cmax, Tmax, AUCinf, t1/2, Vz, CL, F)<br>;Timepoint(s) of evaluation of this end point: Incidence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI) through Day 29 and Week 36

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Progression of COVID-19 through Day 29 as defined by need for attended medical visit* or escalation to higher level of medical care or death (*An attended medical visit includes visit to a hospital emergency room for management of illness or hospitalization for acute management of illness)<br><br>Development of 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 (>24 hours) increase in the level or method of oxygen support required)<br><br>Change from baseline in viral load in nasal secretions measured by qRT-PCR at Day 5, Day 8, and Day 11;Timepoint(s) of evaluation of this end point: Please refer to E.5.2 above.