A Study to Evaluate a Single Intramuscular Dose of Motavizumab to Treat Children With Respiratory Syncytial Virus (RSV) Illness

Study Overview
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Brief Summary
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This was a Phase 2, randomized, double-blind, placebo-controlled, multicenter study to determine the effect of a single 30 mg/kg intramuscular (IM) dose of motavizumab on viral load and motavizumab levels in the upper respiratory tract of children who present with RSV illness but who do not require hospitalization. Using 1:1 randomization, 30 mg/kg motavizumab or placebo will be administered as soon as possible after a child's diagnosis of RSV and his/her eligibility for the study has been confirmed.

Detailed Description
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This was a Phase 2, randomized, double-blind, placebo-controlled, multicenter study to determine the effect of a single 30 mg/kg IM dose of motavizumab on viral load in the upper respiratory tract of children who present with RSV illness but who do not require hospitalization. Participants were randomly assigned in a 1:1 ratio to 30 mg/kg motavizumab or placebo as soon as possible after a child's diagnosis of RSV and his/her eligibility for the study had been confirmed. Randomization was stratified by age (<6 months and greater than or equal to 6 to less than or equal to 12 months of age) and by site. Enrollment of an initial 100 children (50 per treatment group) will take place at multiple sites beginning in the 2006-2007 RSV season. The study was terminated early due to inability to enroll the planned number of participants.

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

Conditions
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Participants Less Than 12 Months of Age With RSV Illness

Intervention / Treatment
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* Biological: Motavizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously healthy Age ≤12 months at the time of randomization Weight ≤10 kg at the time of randomization Gestational age ≥36 weeks RSV illness (must have coryza) documented by a positive RSV test at the time of evaluation Documented stable clinical condition that does not require hospitalization (oxygen saturation ≥ 95%; respiratory rate < 60 breaths/minute in children < 2 months and < 50 breaths/minute in children 2-12 months) Respiratory Distress Assessment Instrument (RDAI) score of ≤ 6 (there can be no more than 1 point assigned for each of the 6 assessment categories) at baseline evaluation Randomization within 4 hours of being evaluated with a positive Binax® RSV test Written informed consent obtained from the participant's parent(s) or legal guardian Exclusion Criteria: Prior receipt of or receiving treatment with steroids (except topical steroids) prior to randomization Prior medically diagnosed RSV infection Prior receipt of or receiving anti-viral treatment for the current episode of RSV infection prior to randomization Any medically significant underlying ongoing chronic illness or organ system dysfunction or other known acute illness, other than the acute RSV infection Known renal impairment, hepatic dysfunction, hematologic abnormalities, seizure or other neurologic disorder or immunodeficiency Requirement for supplemental oxygen (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 arteriosus (PDA), small atrial septal defect (ASD) or small ventricular septal defect (VSD) will be allowed] Previous reaction to intravenous immunoglobulin (IVIG), blood products, or other foreign proteins Prior use of IVIG, RSV-IGIV (RespiGam®), motavizumab or other immunoglobulin products within the past 2 months Prior use of palivizumab (Synagis®) within the past 2 months Currently receiving other investigational agents or have received any other investigational agents within the last 3 months 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

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 of RSV-infected Participants as Measured by Reverse Transcriptase-polymerase Chain Reaction (RT-PCR) at Day 0 | The RSV viral load is measured by real-time RT-PCR in the RSV-infected participants. RSV-infected children are those who are positive for any RSV by RT-PCR of nasal wash aspirates. | Day 0 | 
| RSV Load in the Upper Respiratory Tract of RSV-infected Participants as Measured by RT-PCR at Day 2 | The RSV viral load is measured by real-time RT-PCR in the RSV-infected participants. RSV-infected children are those who are positive for any RSV by RT-PCR of nasal wash aspirates. | Day 2 | 
| RSV Load in the Upper Respiratory Tract of RSV-infected Participants as Measured by RT-PCR at Day 30 | The RSV viral load is measured by real-time RT-PCR in the RSV-infected participants. RSV-infected children are those who are positive for any RSV by RT-PCR of nasal wash aspirates. | Day 30 | 
| RSV Load in the Upper Respiratory Tract of RSV-infected Participants as Measured by RT-PCR at Day 90 | The RSV viral load is measured by real-time RT-PCR in the RSV-infected participants. RSV-infected children are those who are positive for any RSV by RT-PCR of nasal wash aspirates. | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Have Progression of RSV Illness That Requires Subsequent Hospitalization | The percentage of participants who have progression of RSV illness that requires subsequent hospitalization is reported. RSV illness symptomps included fever, coryza, cough, and parental opinion of return to normal health and activity. | From Randomiation (Day 0) Up to Day 30 | 
| Respiratory Assessment Change Score (RACS) Derived From Baseline | The RACS assesses changes in wheezing and retractions as measured by the 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. 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 respiratory rate. The RACS is calculated as arithmetic sum of RDAI score change and of the 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); and Days 2, 7, and 30 | 
| Change From Baseline in Oxygen Saturation Level | Change from baseline in oxygen saturation level is reported. | Baseline (Day 0), Days 2, 7, and 30 | 
| Change in RACS of RSV-infected Outpatient Participants Who Subsequently Required Hospitalization | The RACS assesses changes in wheezing and retractions as measured by the 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 <= 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 the arithmetic sum of the RDAI score change and of the 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 the RACS represents improvement, whereas an increase signifies deterioration. | Baseline (Day 0) to Day 30 | 
| Oxygen Saturation Levels in RSV-infected Outpatient Participants Who Subsequently Required Hospitalization |  | Baseline (Day 0) to Day 30 | 
| Heart Rate of RSV-infected Outpatient Participants Who Subsequently Required Hospitalization |  | Baseline (Day 0) to Day 30 | 
| Respiratory Rate of RSV-infected Outpatient Participants Who Subsequently Required Hospitalization |  | Baseline (Day 0) to Day 30 | 
| Number of Participants Who Required Hospitalization, Intensive Care Unit (ICU) Stay, Supplemental Oxygen, and Mechanical Ventilation | Number of participants who required hospitalization, ICU stay, supplemental oxygen, and mechanical ventilation is reported. | Baseline (Day 0) to Day 90 | 
| Duration of Hospitalization, ICU Stay, Supplemental Oxygen Used, and Mechanical Ventilation Required |  | Baseline (Day 0) to Day 90 | 
| Number of Participants Who Progresses From Upper Respiratory Tract Infection to Lower Respiratory Tract Infection (LRI) | A LRI event is one that has a medical diagnosis of bronchiolitis or pneumonia. In the absence of such a medical diagnosis, the occurrence of LRI events will be determined by the principal investigator after review of the medical record and based on the presence of retractions or lower respiratory tract rhonchi, wheezing, crackles, or rales in children with a positive RSV test. | Baseline (Day 0) to Day 30 | 
| Number of LRI Infected Participants Who Required Hospitalization, ICU Stay, Supplemental Oxygen, Mechanical Ventilation, and Respiratory Medications | Number of LRI infected participants who required hospitalization, ICU stay, supplemental oxygen, mechanical ventilation, and respiratory medications are reported. | Baseline (Day 0) to Day 30 | 
| RACS in Participants With LRI | The RACS assesses changes in wheezing and retractions as measured by RDAI score and changes in respiratory rate. A RDAI score is a measure of 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 <= 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 the arithmetic sum of the RDAI score change and of the 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 the RACS represents improvement, whereas an increase signifies deterioration. RACS in participants with LRI is reported. | From Baseline (Day 0) to Days 2, 7, and 30 | 
| Motavizumab Concentration in Upper Respiratory Tract | Motavizumab concentration in upper respiratory tract (nasal wash aspirates) is reported. | Days 0 (pre-dose), 2, and 30 | 
| Serum Concentration of Motavizumab | Serum concentration of motavizumab is reported. | Days 2, 30, and 90 | 
| Numbers of Participants With Positive Anti-Motavizumab Antibodies | The number of participants with positive serum antibodies to motavizumab are reported. | Days 0 (pre-dose) and 90 | 
| Serum Cytokine Levels | Serum Cytokine Levels are reported. | Days 0 (pre-dose), 30, and 90 | 
| Nasal Wash Cytokine Levels | Nasal wash cytokine levels are reported. | Days 0 (pre-dose), 2, 30, and 90 | 
| 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 administration of study drug (Day 0) through Day 90 | 

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