Safety Study of a Monoclonal Antibody to Respiratory Syncytial Virus (RSV) in Children Hospitalized With RSV Infection

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety of motavizumab (MEDI-524) following a single intravenous dose in children hospitalized with respiratory syncytial virus (RSV).

Detailed Description
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This study was designed as a Phase 1, randomized, double-blind, placebo-controlled, dose-escalation, multicenter clinical study to evaluate the safety, tolerability, serum concentrations, and immunogenicity of a single intravenous dose of motavizumab (MEDI-524) and the effect on the amount of respirtory syncytial virus (RSV) in the respiratory tract (nasopharynx) of otherwise healthy children hospitalized with RSV infection.

Official Title
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A Phase 1, Randomized, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of a Single Intravenous Dose of MEDI-524, a Humanized Enhanced Potency Monoclonal Antibody to Respiratory Syncytial Virus (RSV), in Otherwise Healthy Children Hospitalized With RSV Infection

Conditions
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Respiratory Syncytial Virus Prophylaxis

Intervention / Treatment
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* Biological: Motavizumab
* Biological: Motavizumab
* Biological: Motavizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously healthy Age 24 months and younger at the time of randomization Gestational age of 36 weeks gestation and older Randomization within 24 hours after hospitalization Hospitalized for lower respiratory tract illness (ie, respiratory syncytial virus (RSV) bronchiolitis and/or pneumonia) documented by positive RSV antigen detection or culture in respiratory secretions within 72 hours before randomization Exclusion Criteria: Already received or would receive ribavirin or other anti-viral treatment for the current episode of RSV infection prior to randomization Required intubation for ventilatory support Any medically significant underlying ongoing chronic illness or organ system dysfunction or other known acute illness, other than 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 was allowed) Mechanical ventilation at any time prior to the onset of the current RSV infection Congenital heart disease (children with medically or surgically corrected patent ductus arteriosus [PDA], small atrial septal defect [ASD] or ventricular septal defect [VSD] were allowed) Previous reaction to intravneous immunoglobulin (IVIG), blood products, or other foreign proteins Prior use of IVIG, RSV-IGIV (RespiGam), palivizumab (Synagis), or other immunoglobulin products 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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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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Motavizumab, 3 mg/kg as a single intravenous dose<br>Motavizumab, 3 mg/kg as a single intravenous dose administered on Day 0 | Biological: Motavizumab<br>* Single dose of Motavizumab at a dose of 3 mg/kg administered intravenously (in the vein) on Day 0<br>* Other names: MEDI-524;|
| Experimental: Motavizumab, 15 mg/kg as a single intravenous dose<br>Motavizumab, 15 mg/kg as a single intravenous dose administered on Day 0 | Biological: Motavizumab<br>* Single dose of Motavizumab at a dose of 15 mg/kg administered intravenously (in the vein) on Day 0<br>* Other names: MEDI-524;|
| Experimental: Motavizumab, 30 mg/kg as a single intravenous dose<br>Motavizumab, 30 mg/kg as a single intravenous dose administered on Day 0 | Biological: Motavizumab<br>* Single dose of Motavizumab at a dose of 30 mg/kg administered intravenously (in the vein) on Day 0<br>* Other names: MEDI-524;|
| Placebo Comparator: Placebo, as a single intravenous dose<br>Placebo, as a single intravenous dose administered on Day 0 | Other: Placebo<br>* Single dose of placebo administered intravenously (in the vein) on Day 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Adverse Events Through 30 Days After Dosing | Safety and tolerability of motavizumab (MEDI-524) was measured by adverse events through 30 days after dosing | From the start of treatment to 30 days after dosing | 
| Number of Subjects Reporting Serious Adverse Events Through 30 Days After Dosing | Safety and tolerability of motavizumab (MEDI-524) was measured by serious adverse events through 30 days after dosing | From the start of treatment to 30 days after dosing | 
| The Occurrence of Increased Toxixity Grade From Baseline as Determined by Laboratory Evaluations | Safety and tolerability of motavizumab (MEDI-524) was measured by the occurrence of increased toxicity grade from baseline as determined by laboratory evaluations (complete blood count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, and urinalysis) at baseline and at each study collection time point following dosing | From the start of treatment to 30 days after dosing | 
| To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30 | Mean trough serum concentrations of motavizumab (MEDI-524) were collected on Day 2 and on Day 30. Serum concentrations of MEDI-524 were analysed using a qualified enzyme-linked immunosorbent assay (ELISA). | Day 2 and Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 0 | The serum anti-motavizumab antibody titers were measured in subjects on Day 0 (before dosing). Anti-motavizumab antibody assays were performed at MedImmune using a qualified assay. | Immediately before dosing on Day 0 | 
| To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 30 | The serum anti-motavizumab antibody titers were measured in subjects on Day 30. Anti-motavizumab antibody assays were performed at MedImmune using a qualified assay. | Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MEDI-524, Motavizumab, respiratory syncytial virus, children, intravenous, Rezield