Clinical trial NCT00493285: Safety and Tolerability Study to Evaluate MEDI-534 in Children 6 to < 24 Months of Age
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability,Immunogenicity, and Viral Shedding of MEDI-534, a Live, Attenuated Intranasal Vaccine Against Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV), in Healthy Children 6 to <24 Months of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Respiratory Viral Infections
Respiratory Syncytial Virus Infections
Parainfluenza Virus 3, Human
Keywords: Lower Respiratory Tract Illness
RSV and PIV3 infection
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2007-06-28
Enrollment: 49
Sex: ALL
Minimum age (years): 6
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The overall objective of the MEDI-534 clinical development program is to evaluate the safety, efficacy and tolerability of MEDI-534 for the prevention of serious RSV and PIV3 disease in young infants.

Detailed description: The primary objective of this study is to describe the safety and tolerability of multiple doses of MEDI-534 at 10\^4, 10\^5, or 10\^6 TCID50 when administered to RSV and PIV3 seronegative children 6 to \<24 months of age.

Eligibility criteria: Inclusion Criteria:

* Male or female whose age on the day of randomization is 6 to \<24 months (reached 6th month birthday and not yet reached 2nd year birthday)
* Subject is seronegative to both RSV and PIV3 at screening
* Subject was the product of normal full term pregnancy (defined as \>36 weeks gestation)
* Subject is in general good health
* Subject's legal representative is available by telephone
* Written informed consent and 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, which will be through the end of RSV season (provisionally defined as 01/Apr for the United States) or 180 days after the final dose of study vaccine, whichever is later
* 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 (equal to or greater than 100.4°F \[equal to or greater than 38.0°C\], regardless of route) or lower respiratory illness (Section 4.1.2) within 7 days prior to randomization
* Moderate or severe nasal congestion that in the investigator's opinion could prevent intranasal delivery of vaccine
* 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 such as pain relievers are permitted according to the judgment of the investigator
* Any current or expected receipt of immunosuppressive agents including steroids (2 mg/kg per day of prednisone or its equivalent, or equal to or greater than 20 mg/day if the subject weighs \>10 kg, given daily or on alternate days for equal to or greater than 14 days); children in this category should not receive study vaccine until immunosuppressive agents including corticosteroid therapy have been discontinued for equal to or greater than 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 30 days following final study vaccine dosing
* History of receipt of immunoglobulin products or expected receipt through 30 days after study vaccine dosing
* Receipt of any investigational drug within 60 days prior to randomization or expected receipt through 30 days after final study vaccine dosing
* Receipt of any live virus vaccine (excluding 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 (i.e., non-live) 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 HIV
* Living in the same home or enrolled in the same classroom at day care with infants \<24 months of age (only one child per household may be enrolled into the study)
* Contact with pregnant caregiver
* A household contact who is immunocompromised; the subject should also avoid close contact with immunocompromised individuals for at least 30 days after any study vaccine dose
* A household contact who is a health care provider in contact with immunocompromised patients 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
* 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 Adverse Events (SEs) After Dose 1
timeFrame: Days 0-28 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants With SEs After Dose 2
timeFrame: Days 0-28 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants With SEs After Dose 3
timeFrame: Days 0-28 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants With Adverse Events (AEs) After Dose 1
timeFrame: Days 0-28 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants With AEs After Dose 2
timeFrame: Days 0-28 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants With AEs After Dose 3
timeFrame: Days 0-28 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Subjects With Medically-attended Lower Respiratory Illnesses (MA-LRIs)
timeFrame: Days 0 to 180 days after final dose or the end of the RSV season, whichever was later
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Days 0-28 after any dose
measure: Number of Participants With Significant New Medical Conditions (SNMCs)
timeFrame: Day 0 through 180 days after the final dose or through the end of the RSV season, whichever was later
Secondary outcomes:
measure: Number of Participants Shedding Vaccine-like Virus at Any Time During Study Participation
timeFrame: Days 7, 12, and 28 after each dose and during visits for pre-specified illness symptoms occurring Day 0 through 28-34 days post each dose.
measure: Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 1
timeFrame: Days 7-10 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants Shedding Vaccine-like Virus at 12 Days After Dose 1
timeFrame: Days 12-18 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants Shedding Vaccine-like Virus at 28 Days After Dose 1
timeFrame: Days 28-34 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants With Shedding of Vaccine-like Virus on Any Day During Days 0-28 After Dose 1
timeFrame: Days 0-34 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 2
timeFrame: Days 7-10 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants Shedding Vaccine-like Virus at 12 Days After Dose 2
timeFrame: Days 12-18 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants Shedding Vaccine-like Virus at 28 Days After Dose 2
timeFrame: Days 28-34 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants With Shedding of Vaccine-like Virus on Any Day During Days 0-28 After Dose 2
timeFrame: Days 0-34 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants Shedding Vaccine-like Virus at 7 Days After Dose 3
timeFrame: Days 7-10 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants Shedding Vaccine-like Virus at 12 Days After Dose 3
timeFrame: Days 12-18 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants Shedding Vaccine-like Virus at 28 Days After Dose 3
timeFrame: Days 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants With Shedding of Vaccine-like Virus on Any Day During Days 0-28 After Dose 3
timeFrame: Days 0-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Geometric Mean Titers (GMTs) of Serum Antibodies to RSV at Baseline
timeFrame: Baseline (Day 0 prior to Dose 1)
measure: Geometric Mean Titers (GMTs) of Serum Antibodies to RSV at Day 28 Post Dose 1
timeFrame: Day 28-34 after Dose 1 (Dose 1 was on Day 0)
measure: Geometric Mean Titers (GMTs) of Serum Antibodies to RSV at Day 28 Post Dose 2
timeFrame: Day 28-34 after Dose 2 (Dose 2 was on Day 48-64)
measure: Geometric Mean Titers (GMTs) of Serum Antibodies to RSV at Day 28 Post Dose 3
timeFrame: Day 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies to PIV3 at Baseline
timeFrame: Baseline (Day 0 prior to Dose 1)
measure: Geometric Mean Titers (GMTs) of Serum HAI Antibodies to PIV3 Day 28 Post Dose 1
timeFrame: Day 28-34 after Dose 1 (Dose 1 was on Day 0)
measure: Geometric Mean Titers (GMTs) of Serum HAI Antibodies to PIV3 Day 28 Post Dose 2
timeFrame: Day 28-34 after Dose 2 (Dose 2 was on Day 48-64)
measure: Geometric Mean Titers (GMTs) of Serum HAI Antibodies to PIV3 Day 28 Post Dose 3
timeFrame: Day 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants With Seroresponse to RSV 28 Days After Dose 1
timeFrame: Days 28-34 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants With Seroresponse to RSV 28 Days After Dose 2
timeFrame: Days 28-34 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants With Seroresponse to RSV 28 Days After Dose 3
timeFrame: Days 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
measure: Number of Participants With Seroresponse to PIV3 28 Days After Dose 1
timeFrame: Days 28-34 after Dose 1 (Dose 1 was on Day 0)
measure: Number of Participants With Seroresponse to PIV3 28 Days After Dose 2
timeFrame: Days 28-34 after Dose 2 (Dose 2 was on Day 48-64)
measure: Number of Participants With Seroresponse to PIV3 28 Days After Dose 3
timeFrame: Days 28-34 after Dose 3 (Dose 3 was 48-64 days after Dose 2)
Other outcomes:
Locations:
city: Conway
country: United States
facility: Arkansas Pediatric Research Division
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Pediatric Clinic
state: Arkansas
city: Aurora
country: United States
facility: THe Children's Hospital
state: Colorado
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Palm Beach Gardens
country: United States
facility: Pediatric Partners
state: Florida
city: Dalton
country: United States
facility: North Georgia Clinical Research Center
state: Georgia
city: Chicago
country: United States
facility: University Consultants in Allergy and Immunology
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland, Baltimore
state: Maryland
city: Boston
country: United States
facility: Tufts-New England Medical Center
state: Massachusetts
city: Bridgeton
country: United States
facility: Craig A. Spiegel, MD
state: Missouri
city: Omaha
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Binghamton
country: United States
facility: United Medical Associates
state: New York
city: Mineola
country: United States
facility: Withrop University Hospital
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals case Medical Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Toledo
country: United States
facility: St. Vincent Mercy Medical Center Mercy Children's Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: Primary Physicians Research, Inc.
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Children's Specialty Clinic
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center of Houston Medical School
state: Texas
city: Ogden
country: United States
facility: Bear Care Pediatrics
state: Utah
city: South Jordan
country: United States
facility: Copperview Medical Center
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Vienna
country: United States
facility: Advanced Pediatrics
state: Virginia
city: Spokane
country: United States
facility: Rockwood Clinic Research Center
state: Washington
city: Huntington
country: United States
facility: Marshall University Joan C. Edwards School of Medicine
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia University Health Science Center
state: West Virginia
Study officials:
affiliation: MedImmune LLC
name: Elissa Malkin, D.O.
role: STUDY_DIRECTOR
References:
citation: Bernstein DI, Malkin E, Abughali N, Falloon J, Yi T, Dubovsky F; MI-CP149 Investigators. Phase 1 study of the safety and immunogenicity of a live, attenuated respiratory syncytial virus and parainfluenza virus type 3 vaccine in seronegative children. Pediatr Infect Dis J. 2012 Feb;31(2):109-14. doi: 10.1097/INF.0b013e31823386f1.