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

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

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.

Study Overview

• Status: Completed
• Conditions: RSV Illness in ≤12 Months of Participants
• Intervention / Treatment: Other: Placebo; Biological: Motavizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Herston, Australia, 4029
    • Research Site
• Chile
  • Independencia, Chile
    • Research Site
  • Santiago, Chile
    • Research Site
  • Santiago, Chile, 8360160
    • Research Site
  • Santiago, Chile, 8380418
    • Research Site
• New Zealand
  • Auckland, New Zealand, 2025
    • Research Site
  • Hamilton, New Zealand
    • Research Site
  • Palmerston North, New Zealand, 5301
    • Research Site
• Panama
  • Ciudad de Panama, Panama
    • Research Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Research Site
  • California
    • Long Beach, California, United States, 90806
      • Research Site
    • Orange, California, United States, 92868
      • Research Site
    • San Diego, California, United States, 92123
      • Research Site
  • Florida
    • Jacksonville, Florida, United States
      • Research Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Research Site
    • Oak Lawn, Illinois, United States, 60453
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Research Site
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Research Site
  • New York
    • Brooklyn, New York, United States, 11201
      • Research Site
    • Buffalo, New York, United States, 14222
      • Research Site
    • Mineola, New York, United States, 11501
      • Research Site
    • New Hyde Park, New York, United States, 11040
      • Research Site
    • Rochester, New York, United States, 14642
      • Research Site
    • Syracuse, New York, United States, 13210
      • Research Site
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104-5066
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Research Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: M. Pamela Griffin, M.D., MedImmune LLC

Publications and helpful links

General Publications

• Ramilo O, Lagos R, Saez-Llorens X, Suzich J, Wang CK, Jensen KM, Harris BS, Losonsky GA, Griffin MP; Motavizumab Study Group. Motavizumab treatment of infants hospitalized with respiratory syncytial virus infection does not decrease viral load or severity of illness. Pediatr Infect Dis J. 2014 Jul;33(7):703-9. doi: 10.1097/INF.0000000000000240.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2007
• Primary Completion (Actual): September 17, 2009
• Study Completion (Actual): September 17, 2009

Study Registration Dates

• First Submitted: January 9, 2007
• First Submitted That Met QC Criteria: January 9, 2007
• First Posted (Estimate): January 11, 2007

Study Record Updates

• Last Update Posted (Actual): August 27, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: RSV; Respiratory Syncytial Virus illness
• Other Study ID Numbers: MI-CP141