Clinical trial NCT00767416: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety of MEDI-559 in Healthy 1 to <24 Month-Old Children
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Healthy
Keywords: MEDI-559
Respiratory Syncytial Virus
RSV
Pediatric
Vaccine
respiratory syncytial virus, RSV, pediatric, vaccine
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2008-10-07
Enrollment: 116
Sex: ALL
Minimum age (years): 1
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of solicited symptoms after Dose 1
timeFrame: Through Day 28 after each dose
measure: Incidence of solicited symptoms after Dose 2
timeFrame: Through Day 28 after each dose
measure: Incidence of solicited symptoms after Dose 3
timeFrame: Through Day 28 after each dose
measure: Incidence of adverse events (AEs) after Dose 1
timeFrame: Through Day 28 after each dose
measure: Incidence of AEs after Dose 2
timeFrame: Through Day 28 after each dose
measure: Incidence of AEs after Dose 3
timeFrame: Through Day 28 after each dose
measure: Incidence of medically-attended lower respiratory illnesses (MA-LRIs) after Dose 1
timeFrame: Through Day 28 after each dose
measure: Incidence of MA-LRIs after Dose 2
timeFrame: Through Day 28 after each dose
measure: Incidence of MA-LRIs after Dose 3
timeFrame: Through Day 28 after each dose
measure: Incidence of SAEs
timeFrame: Administration of Dose 1 (Day 0) through Day 28 post final dose
Secondary outcomes:
measure: Incidence of MEDI-559 shedding
timeFrame: Day 7-10 after Dose 1, 2, and 3
measure: Incidence of MEDI-559 shedding
timeFrame: Day 12-18 after Dose 1, 2, and 3
measure: Incidence of MEDI-559 shedding
timeFrame: Day 28-34 post Dose 1, 2, and 3
measure: Post-vaccination seroresponse against RSV
timeFrame: Day 28 post final dose
measure: Phenotypic stability of recovered vaccine-type virus
timeFrame: Day 7-10 post any dose
measure: Phenotypic stability of recovered vaccine-type virus
timeFrame: Day 12-18 post any dose
measure: Phenotypic stability of recovered vaccine-type virus
timeFrame: Day 28-34 post any dose
measure: Genotypic stability of recovered vaccine-type virus
timeFrame: Day 7-10 post any dose
measure: Genotypic stability of recovered vaccine-type virus
timeFrame: Day 12-18 post any dose
measure: Genotypic stability of recovered vaccine-type virus
timeFrame: Day 28-34 post any dose
measure: Incidence of MA-LRIs
timeFrame: Study Day 0 through 365 days post randomization
measure: Incidence of SAEs
timeFrame: Study Day 0 post Dose 1 through 365 days post randomization
measure: Incidence of significant new medical conditions (SNMCs)
timeFrame: Study Day 0 post Dose 1 through 365 days post randomization
Other outcomes:
Locations:
city: Greenville
country: United States
facility: Research Site
state: Alabama
city: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Conway
country: United States
facility: Research Site
state: Arkansas
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Anaheim
country: United States
facility: Research Site
state: California
city: Cypress
country: United States
facility: Research Site
state: California
city: Downey
country: United States
facility: Research Site
state: California
city: Huntington Beach
country: United States
facility: Research Site
state: California
city: Lakewood
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Paramount
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Santa Ana
country: United States
facility: Research Site
state: California
city: Thornton
country: United States
facility: Research Site
state: Colorado
city: Hartford
country: United States
facility: Research Site
state: Connecticut
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orange City
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Dalton
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Fishers
country: United States
facility: Research Site
state: Indiana
city: New Albany
country: United States
facility: Research Site
state: Indiana
city: South Bend
country: United States
facility: Research Site
state: Indiana
city: Ames
country: United States
facility: Research Site
state: Iowa
city: Bardstown
country: United States
facility: Research Site
state: Kentucky
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Paducah
country: United States
facility: Research Site
state: Kentucky
city: Metarie
country: United States
facility: Research Site
state: Louisiana
city: Fredrick
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Fall River
country: United States
facility: Research Site
state: Massachusetts
city: Bridgeton
country: United States
facility: Research Site
state: Missouri
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Brooklyn
country: United States
facility: Research Site
state: New York
city: Endwell
country: United States
facility: Research Site
state: New York
city: Stony Brook
country: United States
facility: Research Site
state: New York
city: Syracuse
country: United States
facility: Research Site
state: New York
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Huber Heights
country: United States
facility: Research Site
state: Ohio
city: Norman
country: United States
facility: Research Site
state: Oklahoma
city: Tulsa
country: United States
facility: Research Site
state: Oklahoma
city: Warwick
country: United States
facility: Research Site
state: Rhode Island
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: Franklin
country: United States
facility: Research Site
state: Tennessee
city: Jackson
country: United States
facility: Research Site
state: Tennessee
city: Johnson City
country: United States
facility: Research Site
state: Tennessee
city: Kingsport
country: United States
facility: Research Site
state: Tennessee
city: Corpus Christi
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Angelo
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Tomball
country: United States
facility: Research Site
state: Texas
city: Layton
country: United States
facility: Research Site
state: Utah
city: St. George
country: United States
facility: Research Site
state: Utah
city: Syracuse
country: United States
facility: Research Site
state: Utah
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Colonial Heights
country: United States
facility: Research Site
state: Virginia
city: Midlothian
country: United States
facility: Research Site
state: Virginia
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Walla Walla
country: United States
facility: Research Site
state: Washington
city: Caguas
country: Puerto Rico
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Joseph Sliman, M.D.
role: STUDY_DIRECTOR
References:
citation: Malkin E, Yogev R, Abughali N, Sliman J, Wang CK, Zuo F, Yang CF, Eickhoff M, Esser MT, Tang RS, Dubovsky F. Safety and immunogenicity of a live attenuated RSV vaccine in healthy RSV-seronegative children 5 to 24 months of age. PLoS One. 2013 Oct 29;8(10):e77104. doi: 10.1371/journal.pone.0077104. eCollection 2013.