Open-Label, Uncontrolled, Single Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of AZD7442 in Pediatric Participants Aged ≥ 29 Weeks Gestational Age to < 18 Years
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Serum Concentrations of AZD7442
研究概览
简要总结
This study will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of AZD7442 administered intramuscularly (IM) or intravenously (IV) in pediatric participants aged ≥ 29 weeks GA to < 18 years.
详细描述
This is a Phase I, open-label, uncontrolled, multi-country, multi-center, single-dose study. Initially, 2 cohorts of participants will be enrolled: 1) participants who are severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) negative at screening and have not knowingly been exposed to a SARS-CoV-2 positive individual (pre-exposure prophylaxis); and 2) participants who are SARS-CoV-2 RT-PCR positive at screening and have mild to moderate COVID-19 symptoms. A third cohort might be added for the treatment of severe COVID-19. If included, this third cohort will include participants who are SARS-CoV-2 positive at screening and have severe COVID-19.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be aged ≥ 29 weeks gestational age (GA) to < 18 years of age.
- •Participant must weigh a minimum of 1.5 kg.
- •Increased risk of severe COVID-19 because of immunocompromised state or one or more comorbid conditions that increase the risk of severe COVID-
- •Increased risk for SARS-CoV-2 infection.
- •Medically stable (disease not requiring significant change in therapy or hospitalization for worsening disease during the one month prior to enrollment).
- •A negative RT-PCR test collected ≤ 3 days prior to Day 1 or a negative rapid SARS-CoV-2 antigen test at screening.
- •No COVID-19 symptoms prior to enrollment within 10 days of dosing.
- •Increased risk for SARS-CoV-2 infection.
- •Increased risk of severe COVID-19 because of immunocompromised state or one or more comorbid conditions that increase the risk of severe COVID-
- •Medically stable (disease not requiring significant change in therapy or hospitalization for worsening disease during the one month prior to enrollment).
- •A positive RT-PCR test collected ≤ 3 days prior to Day 1 or a positive rapid SARS-CoV-2 antigen test at screening.
- •Symptomatic participants must be dosed with IMP no more than 7 days from the self-reported date of first reported sign/symptom.
- •Oxygenation saturation of ≥ 92% obtained at rest within 24 hours prior to Day 1 unless the potential participant regularly receives chronic supplementary oxygen for an underlying lung condition.
- •Note that Cohort 2 will only be included if the indication is progressed in adults.
- •Participants hospitalized with COVID-19 with a time between onset of symptoms and dosing AZD7442 of ≤ 7 days.
- •A positive RT-PCR test collected ≤ 3 days before Day 1 or a positive rapid SARS-CoV-2 antigen test at screening.
- •Spontaneous blood Alanine Aminotransferase (ALT)/Aspartate Transaminase (AST) levels ≤ 5 times the ULN.
- •Glomerular Filtration Rate (GFR) ≥ 30 mL/min/1.73 m
- •Participants will receive IM AZD7442 unless they meet any of the following criteria for IV administration:
- •The participant has severe COVID-
- •Contraindication of intramuscular (IM) dose due to thrombocytopenia, coagulation defects or any other condition that would compromise the absorption of AZD7442 or safety of the participant.
- •Physician considers IV the appropriate route.
排除标准
- •All Cohorts
- •Cohort 1: Significant infection or other acute illnesses including fever on or the day prior to receiving AZD
- •History of SARS-CoV-1 or Middle East Respiratory Syndrome Coronavirus (MERS-CoV).
- •Cohorts 1 and 2: Current need for immediate medical attention or current need for hospitalization.
- •Mechanical ventilation or extracorporeal membrane oxygenation requirement for COVID-
- •History of allergic or reaction to any component of the study drug formulation.
- •History of hypersensitivity, injection/infusion-relation reactions or severe adverse reactions following administration of a monoclonal antibody (mAb).
- •Co-morbidity requiring surgery within 7 days prior to study entry or is deemed life-threatening within 30 days prior to study entry.
- •Prior receipt of convalescent COVID-19 plasma/sera or hyperimmune globulin therapy.
- •Prior receipt of mAb/biologic indicated for the prevention of SARS-CoV-2, treatment of COVID-19, or expected receipt during the period of study follow-up.
- •Prior receipt of a COVID-19 vaccine ≤ 14 days before screening or plan to receive a COVID-19 vaccination ≤ 14 days after IMP administration at study Visit
- •History of alcohol or drug abuse within the past 2 years.
- •Investigational Drugs or Devices: Treatment with investigational drug or device in another clinical trial within the last 30 days or 5 half-lives of the drug (whichever is longer) prior to screening. Note: Participation in observational studies (ie, studies that do not require medication, blood draws, or an additional intervention) is not exclusionary. Interventional trials which do not include investigational drugs (only include approved therapies), or investigational treatment regimens may be considered if the blood draw requirements and study interventions are minimal and not deemed by the Investigator to interfere with completion of the planned study sampling and follow-up.
- •Vulnerable persons (eg, ward of the state, kept in detention).
研究组 & 干预措施
AZD7442
All participants will receive a single dose of AZD7442 on Day 1, either IM (AZD8895 followed by AZD1061) or IV (AZD8895 + AZD1061 concurrently).
干预措施: AZD7442 (Drug)
结局指标
主要结局
Serum Concentrations of AZD7442
时间窗: IM - Day 4, Day 8, Day 11, Day 15 and Day 366; IV - Day 1, Day 4, Day 8, Day 11, Day 15 and Day 366
The serum concentrations of AZD7442 after a single IM or IV dose in pediatric participants were evaluated. The serum concentrations for each scheduled time point were summarized by route of administration using appropriate descriptive statistics, based on the (Pharmacokinetic analysis) PK analysis set.
Maximum Serum Concentration (Cmax)
时间窗: Day 1 to Day 366 or early discontinuation visit (approximately [approx.] 24 months)
The Cmax of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time to Reach Maximum Serum Concentration (Tmax)
时间窗: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
The tmax of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Terminal Half-life (t1/2)
时间窗: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
The t1/2 of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Area Under the Serum Concentration Versus Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last)
时间窗: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
The AUC0-last of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf)
时间窗: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
The AUC0-inf of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time to Last Measurable Concentration (Tlast)
时间窗: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
The tlast of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Percentage of AUC0-inf Extrapolated to Infinity (% AUCex)
时间窗: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
The %AUCex of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Apparent Total Clearance (CL/F)
时间窗: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
The CL/F of AZD7442 after a single IM dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Apparent Volume of Distribution Based on Terminal Phase (Vz/F)
时间窗: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
The Vz/F of AZD7442 after a single IM dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Systemic Clearance (CL)
时间窗: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
The CL of AZD7442 after a single IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Volume of Distribution at Steady State (Vss)
时间窗: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
The Vss of AZD7442 after a single IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Number of Participants With Adverse Events (AE)
时间窗: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
The safety and tolerability of AZD7442 after a single IM or IV dose in pediatric participants was evaluated.
Number of Participants With Adverse Event of Special Interest (AESI)
时间窗: Day 1 to day 366 or early discontinuation visit (approx. 24 months)
Number of pediatric participants with AESI after a single IM or IV dose were evaluated. An AESI is a pre-specified medically significant event that has the potential to be causally associated with a vaccine product.
次要结局
- Number of Participants With Positive Antidrug Antibodies (ADA) Result to AZD7442.(Day 1 to Day 366 or early discontinuation visit (approx. 24 months))
- Cohort 2 - Percentage of Participants With Progression of COVID-19 Through Day 29(Day 1 to Day 366 or early discontinuation visit (approx. 24 months))
- Cohort 2 - Number of Participants With COVID-19 Related Death Occurring After Dosing With IMP Through 90 Days(Day 1 to Day 366 or early discontinuation visit (approx. 24 months))
- Titre of SARS-CoV-2 Neutralizing Antibodies(Day 31 to Day 366 or early discontinuation visit (approx. 24 months))
- Cohort 1 (Prophylaxis) - Number of Participants With SARS-CoV-2 Infections(Day 1 to Day 366 or early discontinuation visit (approx. 24 months))