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

Phase 1

Completed

Conditions: Healthy

Interventions: Biological: MEDI-534, Cohort 2
Other: Placebo, Cohort 2
Biological: MEDI-534, Cohort 4
Other: Placebo, Cohort 1
Biological: MEDI-534, Cohort 3
Other: Placebo, Cohort 3
Biological: MEDI-534, Cohort 5
Biological: MEDI-534, Cohort 1
Other: Placebo, Cohort 4
Other: Placebo, Cohort 5

Registration Number: NCT00686075

Lead Sponsor: MedImmune LLC

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1338

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MEDI-534, Cohort 2	MEDI-534, Cohort 2	Participants aged 6 to \<24 months will receive MEDI-534, 10\^6 TCID50 by intranasal route at Month 0, 2, and 4.
Placebo, Cohort 2	Placebo, Cohort 2	Participants aged 6 to \<24 months will receive placebo matched to MEDI-534, 10\^6 TCID50 by intranasal route at Month 0, 2, and 4.
MEDI-534, Cohort 4	MEDI-534, Cohort 4	Participants aged 2 months will receive MEDI-534, 10\^5 TCID50 by intranasal route at Month 0, 2, and 4.
Placebo, Cohort 1	Placebo, Cohort 1	Participants aged 6 to \<24 months will receive placebo matched to MEDI-534, 10\^5 TCID50 by intranasal route at Month 0, 2, and 4.
MEDI-534, Cohort 3	MEDI-534, Cohort 3	Participants aged 2 months will receive MEDI-534, 10\^4 TCID50 by intranasal route at Month 0, 2, and 4.
Placebo, Cohort 3	Placebo, Cohort 3	Participants aged 2 months will receive placebo matched to MEDI-534, 10\^4 TCID50 by intranasal route at Month 0, 2, and 4.
MEDI-534, Cohort 5	MEDI-534, Cohort 5	Participants aged 2 months will receive MEDI-534, 10\^6 TCID50 by intranasal route at Month 0, 2, and 4.
MEDI-534, Cohort 1	MEDI-534, Cohort 1	Participants aged 6 to less than (\<) 24 months will receive MEDI-534, 10\^5 median tissue culture infectious dose (TCID50) by intranasal route at Month 0, 2, and 4.
Placebo, Cohort 4	Placebo, Cohort 4	Participants aged 2 months will receive placebo matched to MEDI-534, 10\^5 TCID50 by intranasal route at Month 0, 2, and 4.
Placebo, Cohort 5	Placebo, Cohort 5	Participants aged 2 months will receive placebo matched to MEDI-534, 10\^6 TCID50 by intranasal route at Month 0, 2, and 4.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Solicited Symptoms After Dose 2	Within 28 days after Dose 2	Solicited symptoms were predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms included fever \>=100.4 degrees F, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/fussiness, oropharyngeal inflammation (laryngitis), and epistaxis.
Number of Participants With Solicited Symptoms After Dose 3	Within 28 days after Dose 3	Solicited symptoms were predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms included fever \>=100.4 degrees F, runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/fussiness, oropharyngeal inflammation (laryngitis), and epistaxis.
Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 1	Within 28 days after Dose 1	An MA-LRI was a healthcare provider-confirmed diagnosis of 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, and apnea.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Dose 3	Within 28 days after Dose 3	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-Emergent Adverse Events (TEAEs) for Dose 3 are events between administration of Dose 3 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TEAEs (spontaneously reported events) after Dose 3 were reported.
Number of Participants With Solicited Symptoms After Dose 1	Within 28 days after Dose 1	Solicited symptoms were predefined symptoms or events to be specifically inquired about and assessed daily during the 28-day period after vaccine administration. The solicited symptoms included fever greater than or equal to (\>=) 100.4 degrees Fahrenheit (F), runny/stuffy nose, cough, drowsiness, loss of appetite/decreased urine output, irritability/fussiness, oropharyngeal inflammation (laryngitis), and epistaxis.
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) After Dose 1	Within 28 days after Dose 1	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-Emergent Serious Adverse Events (TESAEs) are serious events between administration of Dose 1 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TESAEs (spontaneously reported events) after Dose 1 were reported.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Dose 1	Within 28 days after Dose 1	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events (TEAEs) for Dose 1 are events between administration of Dose 1 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TEAEs (spontaneously reported events) after Dose 1 were reported.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Dose 2	Within 28 days after Dose 2	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-Emergent Adverse Events (TEAEs) for Dose 2 are events between administration of Dose 2 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TEAEs (spontaneously reported events) after Dose 2 were reported.
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) After Dose 2	Within 28 days after Dose 2	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-Emergent Serious Adverse Events (TESAEs) are serious events between administration of Dose 2 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TESAEs (spontaneously reported events) after Dose 2 were reported.
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) After Dose 3	Within 28 days after Dose 3	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-Emergent Serious Adverse Events (TESAEs) are serious events between administration of Dose 3 and up to 28 days after the dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TESAEs (spontaneously reported events) after Dose 3 were reported.
Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 3	Within 28 days after Dose 3	An MA-LRI was a healthcare provider-confirmed diagnosis of 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, and apnea.
Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) After Dose 2	Within 28 days after Dose 2	An MA-LRI was a healthcare provider-confirmed diagnosis of 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, and apnea.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Shed Vaccine-Type Virus	7, 12 and 28 days after Dose 1, 2 and 3	Nasal wash specimens were collected to assess vaccine virus recovery in the upper respiratory tract on 7, 12 and 28 days after each dosing.
Number of Participants With Medically-Attended Lower Respiratory Illnesses (MA-LRIs) Through 365 Days After Randomization	Day 0 to Day 365	An MA-LRI was a healthcare provider-confirmed diagnosis of 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, and apnea. MA-LRIs occurring within 28 days post any dose and after 28 days post any dose were summarized separately.
Percentage of Participants With a Seroresponse to Respiratory Syncytial Virus (RSV) and Human Parainfluenza Virus Type 3 (hPIV3) After Dose 3	Day 28 after Dose 3	Seroresponse was defined as a \>=4-fold rise from Baseline in neutralizing antibody titer, regardless of Baseline serostatus. Respiratory Syncytial Virus (RSV) and hPIV3 antibody titers were determined by using microneutralization assay and hemagglutination inhibition assay, respectively. Clopper-pearson exact confidence interval was reported.
Genotypic Stability of Recovered Vaccine-Type Virus	Within 28 days after any dose	Nasal wash samples with vaccine-type virus were evaluated for genotypic stability, defined as the presence of the entire RSV-Fusion (RSV F) insert based on the RSV F sequence results. If the insert was absent or truncated, the recovered virus was counted as genotypically unstable. Nasal wash samples were categorized as genotypically stable, genotypically unstable or undetermined genotypic stability.
Number of Participants With Significant New Medical Conditions (SNMCs) Through 365 Days After Randomization	Day 0 to Day 365	An SNMC was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. Examples of SNMCs include diabetes, asthma, autoimmune disease (for example, lupus, rheumatoid arthritis), and neurological disease (for example, epilepsy, autism).
Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) Through 365 Days After Randomization	Day 0 to Day 365	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-Emergent Serious Adverse Events (TESAEs) are serious events after administration of drug which were absent before treatment or that worsened relative to pretreatment state. Number of participants with unsolicited TESAEs (spontaneously reported events) within 365 days after randomization were reported.