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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Body Weight-Adjusted Serum Clearance (CL) of Sotrovimab
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study.
入排标准
- 年龄范围
- 0 Days 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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).
排除标准
- •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-
- •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-
- •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).
研究组 & 干预措施
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
干预措施: Sotrovimab (Biological)
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
干预措施: Sotrovimab (Biological)
结局指标
主要结局
Body Weight-Adjusted Serum Clearance (CL) of Sotrovimab
时间窗: Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
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.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESI)
时间窗: Up to Day 29
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.
Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0-inf]) Following Administration of Sotrovimab
时间窗: Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
Blood samples were collected at indicated timepoints and Pharmacokinetic (PK) analysis was performed. PK parameters were determined by population PK modelling method.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs of Special Interest (AESI) Up to Week 36
时间窗: 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.
Apparent Volume of Distribution During Terminal Phase (Vz) Following Administration of Sotrovimab
时间窗: Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
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.
Maximum Observed Concentration (Cmax) Following Administration of Sotrovimab
时间窗: Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
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.
Terminal Elimination Half-Life (T1/2) Following Administration of Sotrovimab
时间窗: Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
Blood samples were collected at indicated timepoints and Pharmacokinetic (PK) analysis was performed. PK parameters were determined by population PK modelling method.
Relative Bioavailability (F) Following Administration of Sotrovimab
时间窗: Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.
Time to Reach Cmax (Tmax) Following Administration of Sotrovimab
时间窗: Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.
Clearance (CL) Following Administration of Sotrovimab
时间窗: Day 1 (End of Infusion), Day 5, 8 and 12, Week 12
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.
次要结局
- 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)