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

Phase 2

Terminated

• Conditions: Participants Less Than 12 Months of Age With RSV Illness
• Interventions: Biological: Motavizumab; Other: Placebo

• Registration Number: NCT00435227
• Lead Sponsor: MedImmune LLC

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2007-02-13
• Study First Submitted QC: 2007-02-13
• Study First Posted: 2007-02-14
• Study Start: 2007-03-20
• Primary Completion: 2008-05-31
• Study Completion: 2008-05-31
• Disposition First Submitted: 2012-07-02
• Disposition First Submitted QC: 2012-07-02
• Disposition First Posted: 2012-07-04
• Results First Submitted: 2021-06-10
• Status Verified: 2021-07
• Results First Submitted QC: 2021-07-22
• Last Update Submitted: 2021-07-22
• Results First Posted: 2021-08-17
• Last Update Posted: 2021-08-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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	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.
RSV Load in the Upper Respiratory Tract of RSV-infected Participants as Measured by RT-PCR at Day 2	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.
RSV Load in the Upper Respiratory Tract of RSV-infected Participants as Measured by RT-PCR at Day 90	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.
RSV Load in the Upper Respiratory Tract of RSV-infected Participants as Measured by RT-PCR at Day 30	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Required Hospitalization, Intensive Care Unit (ICU) Stay, Supplemental Oxygen, and Mechanical Ventilation	Baseline (Day 0) to Day 90	Number of participants who required hospitalization, ICU stay, supplemental oxygen, and mechanical ventilation is reported.
Serum Concentration of Motavizumab	Days 2, 30, and 90	Serum concentration of motavizumab is reported.
Serum Cytokine Levels	Days 0 (pre-dose), 30, and 90	Serum Cytokine Levels are reported.
Percentage of Participants Who Have Progression of RSV Illness That Requires Subsequent Hospitalization	From Randomiation (Day 0) Up to Day 30	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.
Heart Rate of RSV-infected Outpatient Participants Who Subsequently Required Hospitalization	Baseline (Day 0) to Day 30
Number of LRI Infected Participants Who Required Hospitalization, ICU Stay, Supplemental Oxygen, Mechanical Ventilation, and Respiratory Medications	Baseline (Day 0) to Day 30	Number of LRI infected participants who required hospitalization, ICU stay, supplemental oxygen, mechanical ventilation, and respiratory medications are reported.
Motavizumab Concentration in Upper Respiratory Tract	Days 0 (pre-dose), 2, and 30	Motavizumab concentration in upper respiratory tract (nasal wash aspirates) is reported.
Numbers of Participants With Positive Anti-Motavizumab Antibodies	Days 0 (pre-dose) and 90	The number of participants with positive serum antibodies to motavizumab are reported.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	From the administration 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.
Change From Baseline in Oxygen Saturation Level	Baseline (Day 0), Days 2, 7, and 30	Change from baseline in oxygen saturation level is reported.
Change in RACS of RSV-infected Outpatient Participants Who Subsequently Required Hospitalization	Baseline (Day 0) to Day 30	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.
Oxygen Saturation Levels in RSV-infected Outpatient Participants Who Subsequently Required Hospitalization	Baseline (Day 0) to Day 30
Number of Participants Who Progresses From Upper Respiratory Tract Infection to Lower Respiratory Tract Infection (LRI)	Baseline (Day 0) to Day 30	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.
Nasal Wash Cytokine Levels	Days 0 (pre-dose), 2, 30, and 90	Nasal wash cytokine levels are reported.
Respiratory Assessment Change Score (RACS) Derived From Baseline	Baseline (Day 0); and Days 2, 7, and 30	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.
Respiratory Rate of RSV-infected Outpatient Participants Who Subsequently Required Hospitalization	Baseline (Day 0) to Day 30
Duration of Hospitalization, ICU Stay, Supplemental Oxygen Used, and Mechanical Ventilation Required	Baseline (Day 0) to Day 90
RACS in Participants With LRI	From Baseline (Day 0) to Days 2, 7, and 30	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.

Trial Locations

Locations (2)

Research Site; 🇺🇸 Morgantown, West Virginia, United States

West Virginia University Pediactric Center; 🇺🇸 Charleston, West Virginia, United States