A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety of MEDI-559 in Healthy 1 to <24 Month-Old Children

• Incidence of solicited symptoms after Dose 1 [ Time Frame: Through Day 28 after each dose ] [ Designated as safety issue: Yes ]
  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 [ Time Frame: Through Day 28 after each dose ] [ Designated as safety issue: Yes ]
  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 [ Time Frame: Through Day 28 after each dose ] [ Designated as safety issue: Yes ]
  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 adverse events (AEs) after Dose 1 [ Time Frame: Through Day 28 after each dose ] [ Designated as safety issue: Yes ]
  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 [ Time Frame: Through Day 28 after each dose ] [ Designated as safety issue: Yes ]
  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 [ Time Frame: Through Day 28 after each dose ] [ Designated as safety issue: Yes ]
  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 medically-attended lower respiratory illnesses (MA-LRIs) after Dose 1 [ Time Frame: Through Day 28 after each dose ] [ Designated as safety issue: Yes ]
  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 [ Time Frame: Through Day 28 after each dose ] [ Designated as safety issue: Yes ]
  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 3 [ Time Frame: Through Day 28 after each dose ] [ Designated as safety issue: Yes ]
  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 [ Time Frame: Administration of Dose 1 (Day 0) through Day 28 post final dose ] [ Designated as safety issue: Yes ]
  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.
  
  

• Incidence of MEDI-559 shedding [ Time Frame: Day 7-10 after Dose 1, 2, and 3 ] [ Designated as safety issue: No ]
  Number (%) of subjects who shed vaccine-type virus
  
  
• Incidence of MEDI-559 shedding [ Time Frame: Day 12-18 after Dose 1, 2, and 3 ] [ Designated as safety issue: No ]
  Number (%) of subjects who shed vaccine-type virus
  
  
• Incidence of MEDI-559 shedding [ Time Frame: Day 28-34 post Dose 1, 2, and 3 ] [ Designated as safety issue: No ]
  Number (%) of subjects who shed vaccine-type virus
  
  
• Post-vaccination seroresponse against RSV [ Time Frame: Day 28 post final dose ] [ Designated as safety issue: No ]
  Seroresponse is defined as a ≥ 4-fold rise from baseline as measured by microneutralization assay
  
  
• Phenotypic stability of recovered vaccine-type virus [ Time Frame: Day 7-10 post any dose ] [ Designated as safety issue: No ]
  Number (%) of nasal wash samples containing vaccine-type virus that is found to be phenotypically stable
  
  
• Phenotypic stability of recovered vaccine-type virus [ Time Frame: Day 12-18 post any dose ] [ Designated as safety issue: No ]
  Number (%) of nasal wash samples containing vaccine-type virus that is found to be phenotypically stable
  
  
• Phenotypic stability of recovered vaccine-type virus [ Time Frame: Day 28-34 post any dose ] [ Designated as safety issue: No ]
  Number (%) of nasal wash samples containing vaccine-type virus that is found to be phenotypically stable
  
  
• Genotypic stability of recovered vaccine-type virus [ Time Frame: Day 7-10 post any dose ] [ Designated as safety issue: No ]
  Number (%) of nasal wash samples containing vaccine-type virus that is found to be genotypically stable
  
  
• Genotypic stability of recovered vaccine-type virus [ Time Frame: Day 12-18 post any dose ] [ Designated as safety issue: No ]
  Number (%) of nasal wash samples containing vaccine-type virus that is found to be genotypically stable
  
  
• Genotypic stability of recovered vaccine-type virus [ Time Frame: Day 28-34 post any dose ] [ Designated as safety issue: No ]
  Number (%) of nasal wash samples containing vaccine-type virus that is found to be genotypically stable
  
  
• Incidence of MA-LRIs [ Time Frame: Study Day 0 through 365 days post randomization ] [ Designated as safety issue: Yes ]
  Number (%) of subjects with MA-LRIs occurring from Study Day 0 through the end of study
  
  
• Incidence of SAEs [ Time Frame: Study Day 0 post Dose 1 through 365 days post randomization ] [ Designated as safety issue: Yes ]
  Number (%) of subjects with SAEs occurring from Study Day 0 through 365 days post randomization
  
  
• Incidence of significant new medical conditions (SNMCs) [ Time Frame: Study Day 0 post Dose 1 through 365 days post randomization ] [ Designated as safety issue: Yes ]
  Number (%) of subjects with SNMCs from administration of Dose 1 through 365 days post randomization
  
  

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.