A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease

Study Overview
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Brief Summary
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The primary goal was to describe the safety of the investigational product when given monthly to prevent serious respiratory infection among children with significant heart disease.

Detailed Description
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The primary objective was to describe the safety and tolerability of motavizumab when given monthly as prophylaxis against serious RSV infection among children with hemodynamically significant congenital heart disease.

Official Title
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A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of MEDI-524, a Humanized Enhanced Potency Monoclonal Antibody Against Respiratory Syncytial Virus (RSV), in Children With Hemodynamically Significant Congenital Heart Disease

Conditions
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Congenital Heart Disease

Intervention / Treatment
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* Biological: Motavizumab
* 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 have been randomized on or before their 24-month birthday) Documented, hemodynamically significant CHD Unoperated or partially corrected CHD Written informed consent obtained from the patient's parent(s)/legal guardian(s) Note: The following children were not eligible: children with uncomplicated small atrial or ventricular septal defects or patent ductus arteriosus, children with aortic stenosis, pulmonic stenosis, or coarctation of the aorta alone. Children with acyanotic cardiac lesions must have pulmonary hypertension [≥ 40 mmHg measured pressure in the pulmonary artery (PA)] or the need for daily medication to manage CHD. Exclusion Criteria: Unstable cardiac or respiratory status, including cardiac defects so severe that survival was not expected or for which cardiac transplantation was planned or anticipated Hospitalization, unless discharge was anticipated within 21 days Anticipated cardiac surgery within two weeks of randomization Requirement for mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure or other mechanical respiratory or cardiac support Associated non-cardiac anomalies or end organ dysfunction resulting in anticipated survival of less than six months or unstable abnormalities of end organ function Acute respiratory illness, or other acute infection or illness Note: children with any respiratory symptoms must have had a negative RSV test prior to randomization Chronic seizure or evolving or unstable neurologic disorder Known immunodeficiency Mother with HIV infection (unless the child had been proven to be not infected) Known allergy to Ig products Receipt of any polyclonal antibody (for example, Hepatitis B IG, IVIG, VZIG) within 3 months prior to randomization Receipt of palivizumab (Synagis®) within 3 months prior to randomization Use of investigational agents within the past three months (other than investigational agents commonly used during cardiac surgery or the immediate post-operative period, e.g., nitric oxide) Current participation in other investigational protocols of drugs or biological agents Previous participation in MI-CP124 (Season 1)

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 |
| --- | --- |
| Experimental: Motavizumab<br>Motavizumab was administered as an intramuscular injection at 15 mg/kg every 30 days during the RSV season for a maximum of 5 scheduled doses. Additionally, children who underwent cardiac surgery with cardiopulmonary bypass through Study Day 150 were to receive a protocol-specified replacement dose of study drug immediately following the surgery when determined by the physician to be medically stable for an IM injection. | Biological: Motavizumab<br>* 15 mg/kg IM administered at monthly intervals<br>* Other names: Medi-524;|
| Active Comparator: Pailvizumab<br>Palivizumab was administered as an intramuscular injection at 15 mg/kg every 30 days during the RSV season for a maximum of 5 scheduled doses. Additionally, children who underwent cardiac surgery with cardiopulmonary bypass through Study Day 150 were to receive a protocol-specified replacement dose of study drug immediately following the surgery when determined by the physician to be medically stable for an IM injection. | Biological: Palivizumab<br>* 15 mg/kg IM administered at monthly intervals<br>* Other names: Synagis;|

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 Study Day 150 | Adverse events were summarized by system organ class (SOC) and preferred term (using MedDRA Version 11.1) overall. | Days 0-150 | 
| Number of Subjects Reporting Serious Adverse Events Through Study Day 150 | Serious adverse events were those that resulted in death; were life-threatening; resulted in subject hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed above. | Days 0-150 | 
| Number of Subjects Reporting Laboratory Adverse Events |  | Days 0-150 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Subjects Hospitalized for RSV Infection. | An RSV hospitalization was defined as one of the following: 1) Cardiac/respiratory hospitalization with a positive real-time RT-PCR RSV diagnostic test performed at a central laboratory, or 2) New onset of lower respiratory tract symptoms with an objective measure of worsening respiratory status in an already hospitalized subject with a positive real-time RT-PCR RSV diagnostic test performed at a central laboratory (nosocomial RSV hospitalization), or 3) Death demonstrated to be caused by RSV (based on virologic evidence and either clinical history or autopsy). | Days 0-150 | 
| The Number of Subjects With RSV Outpatient MA-LRI for Season 2 Only. | An RSV outpatient MA-LRI was defined as an outpatient medically-attended event designated by the principal investigator as a lower respiratory illness with a positive real-time RT-PCR RSV diagnostic test performed at a central laboratory. | Days 0-150 | 
| Number of Subjects Who Had Anti-motavizumab Antibodies Detected | ECLA-based method | Days 0-150 | 
| Mean Trough Serum Concentration of Motavizumab at Pre-dose 1 | Trough serum concentrations (ug/mL) of motavizumab at pre-dose 1 | Pre-dose 1 | 
| Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 1 | Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 1 | 30 days post-dose 1 | 
| Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 2 | Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 2 | 30 days post-dose 2 | 
| Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 3 | Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 3 | 30 days post-dose 3 | 
| Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 4 | Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 4 | 30 days post-dose 4 | 
| Mean Trough Serum Concentrations of Motavizumab in Subjects Who Underwent Cardiac Surgery With Cardiopulmonary Bypass | Subjects who underwent cardiac surgery with cardiopulmonary bypass through Study Day 150 were to have a blood sample taken for determination of study drug concentrations prior to receipt of another dose of study drug immediately following surgery. | Days 0-150 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Synagis, motavizumab, palivizumab, children, MEDI-524, RSV, congenital hear disease