Clinical trial NCT00435227: A Study to Evaluate a Single Intramuscular Dose of Motavizumab to Treat Children With Respiratory Syncytial Virus (RSV) Illness
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Participants Less Than 12 Months of Age With RSV Illness
Keywords: Respiratory Syncytial Viruses
RSV
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2007-02-14
Enrollment: 12
Sex: ALL
Minimum age (years): 0
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Day 0
measure: RSV Load in the Upper Respiratory Tract of RSV-infected Participants as Measured by RT-PCR at Day 2
timeFrame: Day 2
measure: RSV Load in the Upper Respiratory Tract of RSV-infected Participants as Measured by RT-PCR at Day 30
timeFrame: Day 30
measure: RSV Load in the Upper Respiratory Tract of RSV-infected Participants as Measured by RT-PCR at Day 90
timeFrame: Day 90
Secondary outcomes:
measure: Percentage of Participants Who Have Progression of RSV Illness That Requires Subsequent Hospitalization
timeFrame: From Randomiation (Day 0) Up to Day 30
measure: Respiratory Assessment Change Score (RACS) Derived From Baseline
timeFrame: Baseline (Day 0); and Days 2, 7, and 30
measure: Change From Baseline in Oxygen Saturation Level
timeFrame: Baseline (Day 0), Days 2, 7, and 30
measure: Change in RACS of RSV-infected Outpatient Participants Who Subsequently Required Hospitalization
timeFrame: Baseline (Day 0) to Day 30
measure: Oxygen Saturation Levels in RSV-infected Outpatient Participants Who Subsequently Required Hospitalization
timeFrame: Baseline (Day 0) to Day 30
measure: Heart Rate of RSV-infected Outpatient Participants Who Subsequently Required Hospitalization
timeFrame: Baseline (Day 0) to Day 30
measure: Respiratory Rate of RSV-infected Outpatient Participants Who Subsequently Required Hospitalization
timeFrame: Baseline (Day 0) to Day 30
measure: Number of Participants Who Required Hospitalization, Intensive Care Unit (ICU) Stay, Supplemental Oxygen, and Mechanical Ventilation
timeFrame: Baseline (Day 0) to Day 90
measure: Duration of Hospitalization, ICU Stay, Supplemental Oxygen Used, and Mechanical Ventilation Required
timeFrame: Baseline (Day 0) to Day 90
measure: Number of Participants Who Progresses From Upper Respiratory Tract Infection to Lower Respiratory Tract Infection (LRI)
timeFrame: Baseline (Day 0) to Day 30
measure: Number of LRI Infected Participants Who Required Hospitalization, ICU Stay, Supplemental Oxygen, Mechanical Ventilation, and Respiratory Medications
timeFrame: Baseline (Day 0) to Day 30
measure: RACS in Participants With LRI
timeFrame: From Baseline (Day 0) to Days 2, 7, and 30
measure: Motavizumab Concentration in Upper Respiratory Tract
timeFrame: Days 0 (pre-dose), 2, and 30
measure: Serum Concentration of Motavizumab
timeFrame: Days 2, 30, and 90
measure: Numbers of Participants With Positive Anti-Motavizumab Antibodies
timeFrame: Days 0 (pre-dose) and 90
measure: Serum Cytokine Levels
timeFrame: Days 0 (pre-dose), 30, and 90
measure: Nasal Wash Cytokine Levels
timeFrame: Days 0 (pre-dose), 2, 30, and 90
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From the administration of study drug (Day 0) through Day 90
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Jonesboro
country: United States
facility: Research Site
state: Arkansas
city: Jonesboro
country: United States
facility: Research Site
state: Arkansas
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Orange
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Miami
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Paterson
country: United States
facility: Research Site
state: New Jersey
city: Bronx
country: United States
facility: Research Site
state: New York
city: Brooklyn
country: United States
facility: Research Site
state: New York
city: Buffalo
country: United States
facility: Research Site
state: New York
city: Youngstown
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Charleston
country: United States
facility: West Virginia University Pediactric Center
state: West Virginia
city: Charleston
country: United States
facility: Research Site
state: West Virginia
city: Huntington
country: United States
facility: Research Site
state: West Virginia
city: Morgantown
country: United States
facility: Research Site
state: West Virginia
Study officials:
affiliation: MedImmune LLC
name: M. Pamela Griffin, M.D.
role: STUDY_DIRECTOR
References: