Study of MEDI-524 (Motavizumab) for the Prophylaxis of Serious Respiratory Syncytial Virus (RSV) Disease in High-Risk Children

Study Overview
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Brief Summary
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The primary objective of this study was to compare the safety and efficacy of motavizumab to palivizumab when administered monthly by intramuscular (IM) injection for the reduction of the incidence of RSV hospitalization among children at high risk for serious RSV disease. A secondary objective was to compare the incidence of medically-attended lower respiratory infections (LRIs) between treatment groups.

Detailed Description
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A randomized, double-blind, palivizumab-controlled, multi-center, multi-national trial conducted during 2 Northern Hemisphere RSV seasons with an intervening season in the Southern Hemisphere. Each child only participated during a single RSV season. Approximately 6,600 children at risk for serious RSV disease were to be randomized in a 1:1 ratio to receive either 15 mg/kg of palivizumab or motavizumab by IM injection every 30 days for a total of 5 doses.

Official Title
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A Pivotal Phase 3 Study of MEDI-524 (Numax; Motavizumab), an Enhanced Potency Humanized RSV Monoclonal Antibody, for the Prophylaxis of Serious RSV Disease in High-Risk Children

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: motavizumab (MEDI-524)
* Biological: palivizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 24 months of age or younger at randomization (child must be randomized on or before his/her 24-month birthday) with a diagnosis of chronic lung disease (CLD) of prematurity requiring medical intervention/management (i.e., supplemental oxygen, bronchodilators, or diuretics) within 6 months before randomization OR: 35 weeks gestational age or less at birth and 6 months of age or younger at randomization (children were to be randomized on or before his/her 6-month birthday) Exclusion Criteria: Hospitalization at the time of randomization (unless discharge was anticipated within 10 days) Mechanical ventilation or other mechanical support (including continuous positive airways pressure [CPAP]) Life expectancy < 6 months Active RSV infection (a child with signs/symptoms of respiratory infection must have had negative RSV testing) Known renal impairment Known hepatic dysfunction Chronic seizure or evolving or unstable neurologic disorder Congenital heart disease [CHD] (children with uncomplicated CHD [e.g., patent ductus arterious (PDA), small septal defect] and children with complicated CHD that were currently anatomically and hemodynamically normal could be enrolled) Known immunodeficiency Mother with HIV infection (unless the child has been proven to be not infected) Known allergy to Ig products Receipt of palivizumab, RSV-IGIV, or other RSV-specific monoclonal antibody, or any other polyclonal antibody (for example, hepatitis B IG, IVIG, VZIG) within 3 months prior to randomization Anticipated use of palivizumab or IVIG during the study (blood transfusions permitted) Previous receipt of RSV vaccines Participation in other investigational drug product studies

Ages Eligible for Study
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Maximum Age: 24 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 |
| --- | --- |
| Active Comparator: palivizumab<br>15 mg/kg administered intramuscularly for 5 monthly doses | Biological: palivizumab<br>* Palivizumab, 15 mg/kg administered intramuscularly for 5 monthly doses<br>* Other names: Synagis;|
| Experimental: motavizumab (MEDI-524)<br>15 mg/kg of motavizumab was administered intramuscularly for 5 monthly doses | Biological: motavizumab (MEDI-524)<br>* Motavizumab, 15 mg/kg administered intramuscularly for 5 monthly doses<br>* Other names: MEDI-524;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of RSV Hospitalization (Includes Deaths by RSV) | RSV hospitalization was defined as 1) a respiratory hospitalization with a positive RSV test (primary), 2) a new onset of lower respiratory symptoms in an already hospitalized child, with an objective measure of worsening respiratory status and positive RSV test (nosocomial), or 3) death demonstrated to have been caused by RSV (by autopsy or clinical history and virologic evidence). | Days 0 - 150 | 
| Number of Participants Reporting Any Adverse Events (AEs) | Number of participants reporting one or more AEs | Days 0 - 150 | 
| Number of Participants Reporting Any Related AEs | Number of participants reporting one or more AEs considered related to study drug by the investigator | Days 0 - 150 | 
| Number of Participants Reporting Any Serious Adverse Events (SAEs) | Number of participants reporting one or more SAEs | Days 0 - 150 | 
| Number of Participants Reporting Any Related SAEs | Number of participants reporting one or more SAEs considered related to study drug by the investigator | Days 0 - 150 | 
| Number of Participants Reporting AEs by Highest Severity Grade | Adverse events events were graded by severity; Level 1, 2, 3, or 4 | Days 0 - 150 | 
| Number of Participants Who Discontinued Study Drug Due to AEs |  | Days 0 - 150 | 
| Number of Participants Who Died |  | Days 0 - 150 | 
| Number of Participants Reporting Changes in Vital Signs From Baseline | Vital signs that were in a higher toxicity grade than observed at baseline were to be recorded as AEs | Days 0 - 150 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of Outpatient Medically-attended Lower Respiratory Illness (LRI) | LRI was defined as an event of bronchiolitis or pneumonia or the occurance of a lower tract infectious illness as determined by the PI based on medical history, signs, and symptoms. | Day 0 - 150 | 
| The Incidence of RSV-specific Medically-attended Outpatient Lower Respiratory Illnesses (LRIs) Between Treatment Groups | The RSV-specific LRI was defined as an outpatient medically-attended LRI associated with a positive RSV test and was not inclusive of events that required hospitalization. | Days 0 - 150 | 
| The Incidence of Medically-attended Otitis Media (OM) Infections | Otitis media (OM) was to be recorded as the diagnosis if the following terms were used by the medical care provider: acute OM, acute tympanic membrane (TM) perforation, bulging TM, red TM with fever, OM with effusion, or middle ear effusion. A new episode was defined as a physician-diagnosed OM in either ear after a normal middle ear exam of the ear in question or an episode of acute OM greater than or equal to 21 days after resolution of the previous episode. A diagnosis of persistent middle ear effusion was not to be recorded as a new OM event. | Days 0 - 150 | 
| The Frequency of Prescribed Antibiotics for Medically-attended LRI | The average number of presciptions per event per subject was summarized for each treatment group. | Days 0 - 150 | 
| The Frequency of Prescribed Antibiotics for Medically-attended OM Infections | The average number of presciptions per event per subject was summarized for each treatment group. | Days 0 - 150 | 
| The Number of Participants With Anti-motavizumab Antibodies | Detection of anti-motavizumab antibodies was defined as a titer with a dilution value equal to or greater than 1:10. | Day 0 - 120 | 
| The Serum Concentrations of Motavizumab at Day 0 | Mean serum concentrations of motavizumab at Day 0 | Day 0 | 
| The Trough Serum Concentrations of Motavizumab at 30 Days Post Dose 1 | Mean serum concentrations of motavizumab at 30 days post Dose 1 | 30 days post Dose 1 | 
| The Trough Serum Concentrations of Motavizumab at 30 Days Post Dose 2 | Mean serum concentrations of motavizumab at 30 days post Dose 2 | 30 days post Dose 2 | 
| The Trough Serum Concentrations of Motavizumab at 30 Days Post Dose 3 | Mean serum concentrations of motavizumab at 30 days post Dose 3 | 30 days post Dose 3 | 
| The Trough Serum Concentrations of Motavizumab at 30 Days Post Dose 4 | Mean serum concentrations of motavizumab at 30 days post Dose 4 | 30 days post Dose 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory Syncytial Virus (RSV), motavizumab, palivizumab, Synagis