A Study to Evaluate a Single Intravenous Dose of Motavizumab for the Treatment of Children Hospitalized With Respiratory Syncytial Virus (RSV) Illness

Not Applicable

Completed

Conditions: RSV Illness in ≤12 Months of Participants

Interventions: Other: Placebo
Biological: Motavizumab

Registration Number: NCT00421304

Lead Sponsor: MedImmune LLC

Brief Summary: The primary objective of this study is to describe the effect of a single dose of medication compared to placebo in the upper respiratory tract in previously healthy children less than or equal to 12 months of age who are hospitalized with lower respiratory tract illness.

Detailed Description: The primary objective of this study is to describe the effect of a single 30 mg/kg or 100 mg/kg intravenous (IV) dose of Motavizumab compared to placebo on study drug levels and viral load as measured by cultivatable virus and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in the upper respiratory tract in previously healthy children ≤12 months of age who are hospitalized with lower respiratory tract illness.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 118

Inclusion Criteria

Children must meet all of the following criteria:

Previously healthy
Age less or equal to 12 months at the time of randomization
Gestational age more or equal to 36 weeks
Hospitalized for lower respiratory tract illness (i.e., RSV bronchiolitis and/or pneumonia)
Documented positive RSV test within 48 hours prior to randomization
Randomization within 12 hours of the decision to hospitalize a child for RSV illness
Written informed consent obtained from the participant's parent(s)/legal guardian

Exclusion Criteria

Children must have none of the following:

Prior receipt of or receiving ribavirin or other anti-viral treatment for the current episode of RSV infection prior to randomization
Any use of systemic or inhaled steroids within the past 30 days prior to randomization
Intubation for ventilatory support at randomization
Any medically significant underlying ongoing chronic illness or organ system dysfunction, or other known acute illness except for RSV infection
Known renal impairment, hepatic dysfunction, hematologic abnormalities, seizure or other neurologic disorder or immunodeficiency
Requirement for supplemental oxygen at any time prior to the current RSV infection (brief use of oxygen in the immediate postnatal period to treat a transient condition is allowed)
Mechanical ventilation at any time prior to the onset of the current RSV infection
Congenital heart disease [children with medically or surgically closed patent ductus arteriosis (PDA), small atrial septal defect (ASD) or small ventricular septal defect (VSD) will be allowed]
Previous reaction to IVIG, blood products, or other foreign proteins
Prior use of intravenous immunoglobulin (IVIG), palivizumab (SynagisÒ), or other immunoglobulin products within the past 2 months
Currently receiving other investigational agents or have received any other investigational agents within the 3 months prior to randomization
Prior or current participation in any investigational study with a therapeutic agent or vaccine for RSV

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive a single intravenous (IV) dose of placebo matched to motavizumab on Day 0 of the study.
Motavizumab 30 mg/kg	Motavizumab	Participants will receive a single IV dose of motavizumab 30 mg/kg on Day 0 of the study.
Motavizumab 100 mg/kg	Motavizumab	Participants will receive a single IV dose of motavizumab 100 mg/kg on Day 0 of the study.

Primary Outcome Measures

Name	Time	Method
Motavizumab Concentration in Nasal Wash Aspirates at Day 30	Day 30	Motavizumab concentration in nasal wash aspirates is reported.
Respiratory Syncytial Virus (RSV) Load in the Upper Respiratory Tract as Measured by Quantitative Real Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 0	Day 0	The RSV viral load is measured by cultivatable virus and real-time RT-PCR in the upper respiratory tract in previously healthy children less than or equal to (\<=12) months of age who are hospitalized with lower respiratory tract illness.
RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at Day 3	Day 3	The RSV viral load is measured by cultivatable virus and real-time RT-PCR in the upper respiratory tract in previously healthy children \<=12 months of age who are hospitalized with lower respiratory tract illness.
RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at Day 30	Day 30	The RSV viral load is measured by cultivatable virus and real-time RT-PCR in the upper respiratory tract in previously healthy children \<=12 months of age who are hospitalized with lower respiratory tract illness.
RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at Day 180	Day 180	The RSV viral load is measured by cultivatable virus and real-time RT-PCR in the upper respiratory tract in previously healthy children \<=12 months of age who are hospitalized with lower respiratory tract illness.
Motavizumab Concentration in Nasal Wash Aspirates at Day 7	Day 7	Motavizumab concentration in nasal wash aspirates is reported.
RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at Day 1	Day 1	The RSV viral load is measured by cultivatable virus and real-time RT-PCR in the upper respiratory tract in previously healthy children \<=12 months of age who are hospitalized with lower respiratory tract illness.
RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at Day 2	Day 2	The RSV viral load is measured by cultivatable virus and real-time RT-PCR in the upper respiratory tract in previously healthy children \<=12 months of age who are hospitalized with lower respiratory tract illness.
RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at Day 4	Day 4	The RSV viral load is measured by cultivatable virus and real-time RT-PCR in the upper respiratory tract in previously healthy children \<=12 months of age who are hospitalized with lower respiratory tract illness.
RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at Day 6	Day 6	The RSV viral load is measured by cultivatable virus and real-time RT-PCR in the upper respiratory tract in previously healthy children \<=12 months of age who are hospitalized with lower respiratory tract illness.
RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at Day 90	Day 90	The RSV viral load is measured by cultivatable virus and real-time RT-PCR in the upper respiratory tract in previously healthy children \<=12 months of age who are hospitalized with lower respiratory tract illness.
Motavizumab Concentration in Nasal Wash Aspirates at Day 1	Day 1	Motavizumab concentration in nasal wash aspirates is reported.
RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at Day 5	Day 5	The RSV viral load is measured by cultivatable virus and real-time RT-PCR in the upper respiratory tract in previously healthy children \<=12 months of age who are hospitalized with lower respiratory tract illness.
RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at Day 7	Day 7	The RSV viral load is measured by cultivatable virus and real-time RT-PCR in the upper respiratory tract in previously healthy children \<=12 months of age who are hospitalized with lower respiratory tract illness.
Motavizumab Concentration in Nasal Wash Aspirates at Day 0	Day 0	Motavizumab concentration in nasal wash aspirates is reported.
Motavizumab Concentration in Nasal Wash Aspirates at Day 2	Day 2	Motavizumab concentration in nasal wash aspirates is reported.

Secondary Outcome Measures

Name	Time	Method
Oxygen Saturation Level During RSV Hospitalization	Days 0, 1, 2, 3, 7, and 30	Oxygen saturation level during RSV hospitalization is reported.
Number of Participants With Supplemental Oxygen Use During RSV Hospitalization	From Randomization Day (Day 0) to Discharge Day (up to Day 30)	Number of participants with supplemental oxygen use during RSV hospitalization is reported.
Change From Baseline in Upper Respiratory Tract (Nasal Wash) Cytokine Levels	Baseline (Day 0, pre-dose) through Day 180	Change from baseline in upper respiratory tract (nasal wash) cytokine levels are reported.
Duration of Supplemental Oxygen Use During RSV Hospitalization	From Randomization Day (Day 0) to Discharge Day (up to Day 30)	Duration of supplemental oxygen use during RSV hospitalization is reported.
Number of Participants on Mechanical Ventilation During RSV Hospitalization	From Randomization Day (Day 0) to Discharge Day (up to Day 30)	Number of participants on mechanical ventilation during RSV hospitalization is reported.
Duration of Mechanical Ventilation During RSV Hospitalization	From Randomization Day (Day 0) to Discharge Day (up to Day 30)	Duration of mechanical ventilation during RSV hospitalization is reported.
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs	From the start of study drug (Day 0) through Day 30
Duration of ICU Stay During RSV Hospitalization	From Randomization Day (Day 0) to Discharge Day (up to Day 30)	Duration of ICU stay during RSV hospitalization is reported.
Number of Participants With Detectable Anti-motavizumab Antibodies	Days 0, 180, and 360	Number of participants with detectable anti-motavizumab antibodies are reported. Detection is defined as an anti-motavizumab antibody titer with a dilution value of 1:30 or greater.
Duration of RSV Hospitalization	From Randomization Day (Day 0) to Discharge Day (up to Day 30)	Duration of RSV hospitalization is reported.
Respiratory Assessment Change Score (RACS) Derived From Baseline	Baseline (Day 0), Days 1, 2, 3, 7, and 30	The RACS assesses changes in wheezing and retractions as measured by respiratory distress assessment instrument (RDAI) score and changes in respiratory rate. A RDAI score is a measure of the degree of severity of wheezing and retractions, with score range from 0 to 17; higher scores indicate more severe disease. Respiratory rate is summarized by raw scores and standardized change score. A change in respiratory rate of less than or equal to (\<=) 5% from baseline is counted as a change of 0 units and a change in respiratory rate is assigned 1 point per each 10% change in the respiratory rate. The RACS is calculated as arithmetic sum of RDAI score change and of standardized respiratory rate change (for example, a child showing improvement who had a RDAI of -5 and a respiratory rate change of -2 would have a RACS score of -7). The RACS assessment does not have a minimum and/or maximum scale range. A decrease in RACS represents improvement, whereas an increase signifies deterioration.
Serum Concentration of Motavizumab	Days 1, 7, 90, 180, and 360	Motavizumab concentration in serum is reported.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	From the start of study drug (Day 0) through Day 90	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is 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. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Heart Rate During RSV Hospitalization	Days 0, 1, 2, 3, 7, and 30	Heart rate during RSV hospitalization is reported.
Respiratory Rate During RSV Hospitalization	Days 0, 1, 2, 3, 7, and 30	Respiratory rate during RSV hospitalization is reported.
Number of Participants Admitted to the Intensive Care Unit (ICU)	From Randomization Day (Day 0) to Discharge Day (up to Day 30)	Number of participants admitted to ICU is reported.
Number of Participants With Medically-attended Wheezing Episodes	From randomization (Day 0) through Day 360 (approximately 12 months)	Wheezing episodes are considered medically-attended wheezing episodes if the medical care provider verifies and documents wheezing in the medical record or, in the case of hospitalization, the medical care provider assigns a discharge diagnosis of asthma, bronchiolitis, wheezing, or reactive airway disease. A new wheezing episode is the one that occurs for more than 2 weeks after the diagnosis of the previous episode and the medical opinion is that the wheezing does not represent a persistence of the previous episode. Medically-attended wheezing episodes were calculated and reported in the range of 0 to 9 events.
Change From Baseline in Serum Cytokine Levels	Baseline (Day 0, pre-dose) through Day 360