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

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

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.

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.

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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