A Phase 1/2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Immunogenicity, and Viral Shedding of MEDI-559, a Live Attenuated Intranasal Vaccine Against Respiratory Syncytial Virus in Healthy 1 to <24 Month-Old Children
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 116
- 试验地点
- 77
- 主要终点
- Incidence of adverse events (AEs) after Dose 1
研究概览
简要总结
The primary objective of this study is to describe the 28-day post-final dose safety and tolerability of three doses of MEDI-559 at 10^5 FFU when administered to healthy RSV seronegative children 1 to <24 months of age.
详细描述
This is a randomized, double-blind, placebo-controlled, multi-dose, Phase 1/2a multi-center trial to evaluate the safety, tolerability, viral shedding, immunogenicity, and genotypic and phenotypic stability of MEDI-559 in RSV seronegative infants 5 to <24 months of age and in infants 1 to <3 months of age regardless of baseline serostatus. The primary objective of this study is to describe the 28-day post-final dose safety and tolerability of three doses of MEDI-559 at 10^5 FFU when administered to healthy RSV seronegative children 5 to <24 months of age and to healthy infants 1 to <3 months of age regardless of baseline serostatus.
MEDI-559 will be administered at a dose of 10^5 fluorescent focus units (FFU) on a 0, 2, and 4 month schedule to two cohorts of subjects in a step-wise fashion. The target sample size for this study is 320 subjects, with 160 subjects 5 to <24 months of age enrolled into Cohort 1 and 160 subjects 1 to <3 months of age enrolled into Cohort 2. Each cohort will be randomized 1:1 (MEDI-559 to placebo) and stratified by site. Cohort 1 will initiate dosing at 10^5 FFU MEDI-559. Blinded safety data from the first 40 subjects enrolled in Cohort 1 for the 28 days following administration of the first dose of vaccine will be reviewed. If no safety concerns are noted, Cohort 2 will initiate dosing at 10^5 FFU. Enrollment into Cohort 2 will be halted after approximately 40 subjects have been randomized, and blinded safety data will be reviewed through 28 days post Dose 1. If no safety concerns are noted, the remainder of Cohort 2 will be enrolled. All subjects will be followed through 365 days after randomization to ensure that each subject has been followed through an RSV season.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Month 至 23 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female whose age on the day of randomization falls within one of the two age cohorts: Cohort 1: 5 to <24 months (reached their 5th month birthday but not yet reached their 2nd year birthday); Cohort 2: 1 to < 3 months (>28 days of age and not yet reached their 3rd month birthday)
- •Cohort 1 only: Subject is seronegative to RSV at screening
- •Subject was the product of normal full term pregnancy (defined as 36-42 weeks gestation)
- •Subject is in general good health
- •Written informed consent and HIPAA authorization (if applicable) obtained from the subject's legal representative
- •Subject's legal representative is willing and able to bring the subject to the study site for evaluation of respiratory illness in accordance with the protocol
排除标准
- •Any fever (≥ 100.4°F [≥ 38.0°C]), regardless of route within 7 days prior to randomization
- •Acute illness (defined as the presence of moderate or severe signs and symptoms) at the time of randomization
- •Moderate or severe nasal congestion that in the investigator's opinion could prevent intranasal delivery of vaccine
- •Cohort 1 only: weight ≤ 5th percentile for age on the day of randomization
- •Cohort 2 only: history of low birth weight (ie, <2500 grams at birth) or weight ≤ 5th percentile for age on the day of randomization
- •Living in the same home or enrolled in the same classroom at day care with infants <6 months of age within 28 days after each dose (only one child per household may be enrolled into the study)
- •Contact with pregnant caregiver within 28 days after each dose
- •Living in a household with someone who is immunocompromised within 28 days after each dose; the subject should also avoid close contact with immunocompromised individuals for at least 28 days after each study vaccine dosing
- •Living in a household with someone who works in the healthcare field and who has direct patient care responsibilities within 28 days after each dose
- •Living in a household with someone who is a day care provider or preschool teacher for children <6 months of age within 28 days after each dose
结局指标
主要结局
Incidence of adverse events (AEs) after Dose 1
时间窗: Through Day 28 after each dose
As defined by the ICH Guideline for Good Clinical Practice, an AE is: Any untoward medical occurrence in a participant or clinical investigations subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Incidence of AEs after Dose 2
时间窗: Through Day 28 after each dose
As defined by the ICH Guideline for Good Clinical Practice, an AE is: Any untoward medical occurrence in a participant or clinical investigations subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Incidence of AEs after Dose 3
时间窗: Through Day 28 after each dose
As defined by the ICH Guideline for Good Clinical Practice, an AE is: Any untoward medical occurrence in a participant or clinical investigations subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Incidence of solicited symptoms after Dose 1
时间窗: Through Day 28 after each dose
Solicited symptoms are predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms for this study include: fever \>100.4°F (\>38.0 °C) regardless of route, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/Fussiness, oropharyngeal irritation (laryngitis), epistaxis
Incidence of solicited symptoms after Dose 2
时间窗: Through Day 28 after each dose
Solicited symptoms are predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms for this study include: fever \>100.4°F (\>38.0 °C) regardless of route, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/Fussiness, oropharyngeal irritation (laryngitis), epistaxis
Incidence of solicited symptoms after Dose 3
时间窗: Through Day 28 after each dose
Solicited symptoms are predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms for this study include: fever \>100.4°F (\>38.0 °C) regardless of route, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/Fussiness, oropharyngeal irritation (laryngitis), epistaxis
Incidence of MA-LRIs after Dose 3
时间窗: Through Day 28 after each dose
An MA-LRI is defined as a health care provider confirmed diagnosis of any one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, apnea
Incidence of medically-attended lower respiratory illnesses (MA-LRIs) after Dose 1
时间窗: Through Day 28 after each dose
An MA-LRI is defined as a health care provider confirmed diagnosis of any one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, apnea
Incidence of MA-LRIs after Dose 2
时间窗: Through Day 28 after each dose
An MA-LRI is defined as a health care provider confirmed diagnosis of any one or more of the following events: wheezing, pneumonia, croup (laryngotracheobronchitis), rhonchi (not cleared with cough or suctioning), rales (not cleared with cough or suctioning), bronchitis, bronchiolitis, apnea
Incidence of SAEs
时间窗: Administration of Dose 1 (Day 0) through Day 28 post final dose
An SAE is any adverse event that results in any of the following outcomes: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital anomaly/birth defect (in the offspring of a subject); an important medical event that may not result in death, threaten life or require hospitalization may be considered a serious adverse event when, based upon appropriate medical judgment, it may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above.
次要结局
- Phenotypic stability of recovered vaccine-type virus(Day 28-34 post any dose)
- Incidence of significant new medical conditions (SNMCs)(Study Day 0 post Dose 1 through 365 days post randomization)
- Incidence of SAEs(Study Day 0 post Dose 1 through 365 days post randomization)
- Genotypic stability of recovered vaccine-type virus(Day 28-34 post any dose)
- Incidence of MA-LRIs(Study Day 0 through 365 days post randomization)
- Incidence of MEDI-559 shedding(Day 28-34 post Dose 1, 2, and 3)
- Post-vaccination seroresponse against RSV(Day 28 post final dose)