Clinical trial NCT00686075: A Study to Evaluate the Safety, Tolerability, Immunogenicity and Vaccine-like Viral Shedding of MEDI-534, Against Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3), in Healthy 6 to <24 Month-old Children and in 2 Month-old Infants
Official title: A Phase 1/2a, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Tolerability, Immunogenicity and Vaccine-like Viral Shedding of MEDI-534, a Live, Attenuated Intranasal Vaccine Against Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3), in Healthy 6 to < 24 Month-old Children and in 2 Month-old Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Healthy
Keywords: Respiratory Syncytial Virus (RSV)
Parainfluenza Virus Type 3 (PIV3)
MEDI-534
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2008-05-29
Enrollment: 1338
Sex: ALL
Minimum age (years): 2
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary objective of this study is to describe the safety and tolerability of multiple doses of MEDI-534 in children 6 to less than (\<) 24 months of age and in infants 2 months of age.

Detailed description: This is a Phase 1/2a, randomized, double-blind, placebo-controlled, dose-escalation, multicenter study to evaluate the safety and tolerability of multiple doses of MEDI-534 at 10\^5 or 10\^6 median tissue culture infectious dose (TCID50) in RSV and PIV3 seronegative children 6 to \<24 months of age and at dosages of 10\^4, 10\^5 or 10\^6 TCID50 in unscreened infants 2 months of age.

Eligibility criteria: Inclusion Criteria:

* Male or female whose age on the day of randomization falls within one of the two age groups:

  6 to less than (\<) 24 months (more than \[\>\] 6 months of age and not yet reached their 2nd year birthday), Cohorts 1 and 2 2 months (+/- 4 weeks), Cohorts 3, 4, and 5
* Cohorts 1 and 2 only: Subject is seronegative to both Respiratory Syncytial Virus (RSV) and human Parainfluenza Virus Type 3 (hPIV3) at Screening
* Subject whose gestational age was greater than or equal to (\>=) 36 weeks
* Subject is in general good health with normal growth (that is, body weight greater than (\>) third percentile per world health organization \[WHO\] simplified weight-per-age field tables
* Subject's legal representative is available by telephone
* Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization (if applicable) obtained from the subject's legal representative
* Subject's legal representative is able to understand and comply with the requirements of the protocol as judged by the investigator
* Subject is available to complete the follow-up period 1-year after receipt of the first dose of study vaccine
* Subject's legal representative must be 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 degrees Fahrenheit \[\>=38.0 degrees Celsius\], regardless of route) or lower respiratory illness within 7 days prior to randomization
* Moderate or severe nasal congestion that in the investigator's opinion could interfere with intranasal delivery of study vaccine
* Acute illness (defined as the presence of moderate or severe signs and symptoms) at the time of randomization
* Any drug therapy (chronic or other) within 7 days prior to randomization or expected receipt through the protocol-specified blood collection 28 days after each study vaccine dosing, except that infrequent use of over-the-counter medications for the systemic treatment of common childhood symptoms (that is, pain relievers, decongestants or cough suppressants) are permitted according to the judgment of the investigator
* Any current or expected receipt of immunosuppressive agents including steroids (\>=2 milligram per kilogram \[mg/kg\] per day of prednisone or its equivalent, or \>=20 milligram per day \[mg/day\] if the subject weighs \>10 kilogram \[kg\], given daily or on alternate days for \>=14 days); children in this category should not receive study vaccine until immunosuppressive agents including corticosteroid therapy have been discontinued for \>=30 days; the use of topical steroids is permitted according to the judgment of the investigator
* History of receipt of blood transfusion or expected receipt through the protocol-specified blood collection at 28 days after final study dosing
* History of receipt of immunoglobulin products or expected receipt through the protocol-specified blood collection at 28 days after final study dosing
* Receipt of any investigational drug within 60 days prior to randomization or expected receipt through 180 days after final study dosing
* Receipt of any live virus vaccine (excluding oral polio vaccine and rotavirus vaccine) within 28 days prior to randomization or expected receipt within a 28-day window around any study vaccine dose
* Receipt of any inactivated (that is, non-live) vaccine or oral polio vaccine or rotavirus vaccine within 14 days prior to randomization or expected receipt within a 14-day window around any study vaccine dose
* Known or suspected immunodeficiency, including human immunodeficiency virus (HIV) infection
* Expected to be living in the same home or enrolled in the same classroom at day care with infants \<6 months within 28 days after each dose
* Living in a household with another child who is concurrently enrolled in a study of a live viral vaccine (including this study)
* Expected contact with a pregnant caregiver within 28 days after each dose
* A household contact who is immunocompromised; the subject should also avoid close contact with immunocompromised individuals for at least 28 days after any study vaccine dose
* Expected household contact within 28 days after each dose with a health care provider for immunocompromised subjects or who is a day care provider for infants under the age of 6 months
* History of allergic reaction to any component of the study vaccine
* Previous medical history, or evidence, of an intercurrent or chronic illness that, in the opinion of the investigator, may compromise the safety of the subject
* Known or suspected active or chronic hepatitis infection
* History of medical diagnosis of asthma, reactive airway disease, wheezing requiring medication, cystic fibrosis, bronchopulmonary dysplasia, chronic pulmonary disease, medically confirmed apnea, hospitalization for respiratory illness or mechanical ventilation for respiratory illness (excludes elective mechanical ventilation during surgery for subjects in Cohorts 1 and 2)
* Family member or household contact who is an employee of the research center or otherwise involved with the conduct of the study
* Any condition that, in the opinion of the investigator, might interfere with study vaccine evaluation.

Primary outcomes:
measure: Number of Participants With Solicited Symptoms After Dose 1
timeFrame: Within 28 days after Dose 1
measure: Number of Participants With Solicited Symptoms After Dose 2
timeFrame: Within 28 days after Dose 2
measure: Number of Participants With Solicited Symptoms After Dose 3
timeFrame: Within 28 days after Dose 3
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Dose 1
timeFrame: Within 28 days after Dose 1
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Dose 2
timeFrame: Within 28 days after Dose 2
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Dose 3
timeFrame: Within 28 days after Dose 3
measure: Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) After Dose 1
timeFrame: Within 28 days after Dose 1
measure: Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) After Dose 2
timeFrame: Within 28 days after Dose 2
measure: Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) After Dose 3
timeFrame: Within 28 days after Dose 3
measure: Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 1
timeFrame: Within 28 days after Dose 1
measure: Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 2
timeFrame: Within 28 days after Dose 2
measure: Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 3
timeFrame: Within 28 days after Dose 3
Secondary outcomes:
measure: Number of Participants Who Shed Vaccine-Type Virus
timeFrame: 7, 12 and 28 days after Dose 1, 2 and 3
measure: Percentage of Participants With a Seroresponse to Respiratory Syncytial Virus (RSV) and Human Parainfluenza Virus Type 3 (hPIV3) After Dose 3
timeFrame: Day 28 after Dose 3
measure: Genotypic Stability of Recovered Vaccine-Type Virus
timeFrame: Within 28 days after any dose
measure: Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) Through 365 Days After Randomization
timeFrame: Day 0 to Day 365
measure: Number of Participants With Significant New Medical Conditions (SNMCs) Through 365 Days After Randomization
timeFrame: Day 0 to Day 365
measure: Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) Through 365 Days After Randomization
timeFrame: Day 0 to Day 365
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Bentonville
country: United States
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state: Arkansas
city: Little Rock
country: United States
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state: Arkansas
city: Anaheim
country: United States
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state: California
city: Anaheim
country: United States
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state: California
city: Bell Gardens
country: United States
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state: California
city: Downey
country: United States
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state: California
city: Lakewood
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state: California
city: Long Beach
country: United States
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state: California
city: Paramount
country: United States
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state: California
city: San Diego
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state: California
city: West Covina
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state: California
city: Thornton
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state: Colorado
city: Gainesville
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city: Tampa
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city: Dalton
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state: Georgia
city: Chicago
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state: Illinois
city: Kansas City
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state: Kansas
city: Topeka
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state: Kansas
city: Lexington
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state: Kentucky
city: Paducah
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state: Kentucky
city: Shreveport
country: United States
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state: Louisiana
city: St. Paul
country: United States
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state: Minnesota
city: Bridgeton
country: United States
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state: Missouri
city: Omaha
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state: Nebraska
city: Omaha
country: United States
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state: Nebraska
city: Las Vegas
country: United States
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state: Nevada
city: Brooklyn
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state: New York
city: Johnson City
country: United States
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state: New York
city: Lake Success
country: United States
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city: Stony Brook
country: United States
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state: New York
city: Syracuse
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city: New Bern
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state: North Carolina
city: Cincinnati
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state: Ohio
city: Gresham
country: United States
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state: Oregon
city: Pittsburgh
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state: Pennsylvania
city: Sellersville
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city: Jackson
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state: Tennessee
city: Amarillo
country: United States
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state: Texas
city: Dallas
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city: Houston
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state: Texas
city: Poteet
country: United States
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state: Texas
city: San Antonio
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state: Texas
city: San Antonio
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state: Texas
city: San Antonio
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city: Tomball
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state: Texas
city: Layton
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state: Utah
city: Orem
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state: Utah
city: St. George
country: United States
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state: Utah
city: Midlothian
country: United States
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state: Virginia
city: Huntington
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state: West Virginia
city: Garran
country: Australia
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state: Australian Capital Territory
city: Herston
country: Australia
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state: Queensland
city: North Adelaide
country: Australia
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state: South Australia
city: Subiaco
country: Australia
facility: Research Site
state: Western Australia
city: Passo Fundo-RS
country: Brazil
facility: Research Site
state: Rio Grande do Sul
city: Sao Paulo
country: Brazil
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state: SP
city: Porto alegre - RS
country: Brazil
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city: Porto Alegre/RS
country: Brazil
facility: Research Site
city: Ribeirao Preto - SP
country: Brazil
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city: Sao Paulo - SP
country: Brazil
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city: São Paulo
country: Brazil
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city: Brampton
country: Canada
facility: Research Site
state: Ontario
city: Saskatoon
country: Canada
facility: Research Site
state: Saskatchewan
city: Helsinki
country: Finland
facility: Research Site
city: Jarvenpaa
country: Finland
facility: Research Site
city: Kokkola
country: Finland
facility: Research Site
city: Kuopio
country: Finland
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city: Lahti
country: Finland
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city: Oulu
country: Finland
facility: Research Site
city: Pori
country: Finland
facility: Research Site
city: Tampere
country: Finland
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city: Turku
country: Finland
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Netanya
country: Israel
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
state: Gauteng
city: Pretoria
country: South Africa
facility: Research Site
state: Gauteng
city: Belle Ville Cape Town
country: South Africa
facility: Research Site
state: Western Cape
city: Cape Town
country: South Africa
facility: Research Site
state: Western Cape
city: Almeria
country: Spain
facility: Research Site
state: Andalucia
city: Almeria
country: Spain
facility: Research Site
state: Andalucia
city: Almeria
country: Spain
facility: Research Site
state: Andalucia
city: Jerez de la Frontera
country: Spain
facility: Research Site
state: Andalucía
city: Barcelona
country: Spain
facility: Research Site
state: Cataluna
city: Catarroja
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: La Eliana, Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Santiago de Compostela
country: Spain
facility: Research Site
state: Galicia
city: Madrid
country: Spain
facility: Research Site
state: Madrid, Communidad de
city: San Sebastian
country: Spain
facility: Research Site
state: Pais Vasco
city: Esplugues de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Elissa Malkin, D.O.
role: STUDY_DIRECTOR
References:
citation: Yang CF, Wang CK, Malkin E, Schickli JH, Shambaugh C, Zuo F, Galinski MS, Dubovsky F; Study Group; Tang RS. Implication of respiratory syncytial virus (RSV) F transgene sequence heterogeneity observed in Phase 1 evaluation of MEDI-534, a live attenuated parainfluenza type 3 vectored RSV vaccine. Vaccine. 2013 Jun 10;31(26):2822-7. doi: 10.1016/j.vaccine.2013.04.006. Epub 2013 Apr 16.