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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate a Single Intravenous Dose of Motavizumab (MEDI-524), a Humanized Enhanced Potency Monoclonal Antibody Against Respiratory Syncytial Virus (RSV), for the Treatment of Children Hospitalized With RSV Illness

Conditions
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RSV Illness in ≤12 Months of Participants

Intervention / Treatment
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* Biological: Motavizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 0 Months
Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive a single intravenous (IV) dose of placebo matched to motavizumab on Day 0 of the study. | Other: Placebo<br>* A single IV dose of placebo matched to motavizumab will be administered on Day 0 of the study.<br>|
| Experimental: Motavizumab 30 mg/kg<br>Participants will receive a single IV dose of motavizumab 30 mg/kg on Day 0 of the study. | Biological: Motavizumab<br>* A single IV dose of motavizumab 30 mg/kg or 100 mg/kg will be administered on Day 0 of the study.<br>* Other names: MEDI-524;|
| Experimental: Motavizumab 100 mg/kg<br>Participants will receive a single IV dose of motavizumab 100 mg/kg on Day 0 of the study. | Biological: Motavizumab<br>* A single IV dose of motavizumab 30 mg/kg or 100 mg/kg will be administered on Day 0 of the study.<br>* Other names: MEDI-524;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Day 0 | 
| RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at 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. | Day 1 | 
| RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at 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. | Day 2 | 
| RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at 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. | Day 3 | 
| RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at 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. | Day 4 | 
| RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at 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. | Day 5 | 
| RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at 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. | Day 6 | 
| RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at 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. | Day 7 | 
| RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at 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. | Day 30 | 
| RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at 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. | Day 90 | 
| RSV Load in the Upper Respiratory Tract as Measured by Quantitative RT-PCR at 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. | Day 180 | 
| Motavizumab Concentration in Nasal Wash Aspirates at Day 0 | Motavizumab concentration in nasal wash aspirates is reported. | Day 0 | 
| Motavizumab Concentration in Nasal Wash Aspirates at Day 1 | Motavizumab concentration in nasal wash aspirates is reported. | Day 1 | 
| Motavizumab Concentration in Nasal Wash Aspirates at Day 2 | Motavizumab concentration in nasal wash aspirates is reported. | Day 2 | 
| Motavizumab Concentration in Nasal Wash Aspirates at Day 7 | Motavizumab concentration in nasal wash aspirates is reported. | Day 7 | 
| Motavizumab Concentration in Nasal Wash Aspirates at Day 30 | Motavizumab concentration in nasal wash aspirates is reported. | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of RSV Hospitalization | Duration of RSV hospitalization is reported. | From Randomization Day (Day 0) to Discharge Day (up to Day 30) | 
| Respiratory Assessment Change Score (RACS) Derived From Baseline | 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. | Baseline (Day 0), Days 1, 2, 3, 7, and 30 | 
| Oxygen Saturation Level During RSV Hospitalization | Oxygen saturation level during RSV hospitalization is reported. | Days 0, 1, 2, 3, 7, and 30 | 
| Heart Rate During RSV Hospitalization | Heart rate during RSV hospitalization is reported. | Days 0, 1, 2, 3, 7, and 30 | 
| Respiratory Rate During RSV Hospitalization | Respiratory rate during RSV hospitalization is reported. | Days 0, 1, 2, 3, 7, and 30 | 
| Number of Participants With Supplemental Oxygen Use During RSV Hospitalization | Number of participants with supplemental oxygen use during RSV hospitalization is reported. | From Randomization Day (Day 0) to Discharge Day (up to Day 30) | 
| Duration of Supplemental Oxygen Use During RSV Hospitalization | Duration of supplemental oxygen use during RSV hospitalization is reported. | From Randomization Day (Day 0) to Discharge Day (up to Day 30) | 
| Number of Participants on Mechanical Ventilation During RSV Hospitalization | Number of participants on mechanical ventilation during RSV hospitalization is reported. | From Randomization Day (Day 0) to Discharge Day (up to Day 30) | 
| Duration of Mechanical Ventilation During RSV Hospitalization | Duration of mechanical ventilation during RSV hospitalization is reported. | From Randomization Day (Day 0) to Discharge Day (up to Day 30) | 
| Number of Participants Admitted to the Intensive Care Unit (ICU) | Number of participants admitted to ICU is reported. | From Randomization Day (Day 0) to Discharge Day (up to Day 30) | 
| Duration of ICU Stay During RSV Hospitalization | Duration of ICU stay during RSV hospitalization is reported. | From Randomization Day (Day 0) to Discharge Day (up to Day 30) | 
| Number of Participants With Medically-attended Wheezing Episodes | 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. | From randomization (Day 0) through Day 360 (approximately 12 months) | 
| Serum Concentration of Motavizumab | Motavizumab concentration in serum is reported. | Days 1, 7, 90, 180, and 360 | 
| Number of Participants With Detectable Anti-motavizumab Antibodies | 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. | Days 0, 180, and 360 | 
| Change From Baseline in Serum Cytokine Levels |  | Baseline (Day 0, pre-dose) through Day 360 | 
| Change From Baseline in Upper Respiratory Tract (Nasal Wash) Cytokine Levels | Change from baseline in upper respiratory tract (nasal wash) cytokine levels are reported. | Baseline (Day 0, pre-dose) through Day 180 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | 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. | From the start of study drug (Day 0) through Day 90 | 
| Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs |  | From the start of study drug (Day 0) through Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory Syncytial Virus illness, RSV