Open-Label, Dose-Escalation Study of 2 to 5 IM Doses of MEDI-524 at 3 mg/kg or 15 mg/kg; Children to be Followed for 90 Days After Their Last Dose of MEDI-524

Study Overview
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Brief Summary
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MEDI-524 given for up to 5 doses at 3 and 15 mg/kg to high-risk children appeared to be safe and well tolerated.

Detailed Description
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This study is designed to describe the safety, tolerability, immunogenicity, and pharmacokinetics of escalating, repeated IM injections (the intended route of administration for immunoprophylaxis) of MEDI-524, initially in children £6 months old with a history of prematurity (³32 to £35 weeks gestation, without BPD), one of the target populations of infants at high risk for serious RSV disease.

Official Title
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A Phase 1/2, Open-Label, Repeat-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Immunogenicity, and Pharmacokinetics of MEDI-524, a Humanized Enhanced Potency Monoclonal Antibody Against Respiratory Syncytial Virus (RSV), in Children at Risk for Serious RSV Disease

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: Medi-524


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All male or female children must have met all the following criteria: [Groups 1, 2, and 3] The child must have been born at ³32 to £35 weeks gestation and have been £6 months of age at the time of entry into the study (child must have been entered on or before their 6-month birthday) or [Group 3 only] The child must have been £24 months of age at the time of entry into the study (child must have been entered on or before their 24-month birthday) and diagnosed with BPD, with stable or decreasing doses of diuretics, steroids, or bronchodilators within the previous 6 months The child must have been in general good health at the time of entry The child's parent or legal guardian must have provided written informed consent; and The child must have been able to complete the follow-up visits through 90 days following last injection of MEDI-524 Parent/legal guardian of patient must have had available telephone access Exclusion Criteria: Children must have had none of the following: Hospitalization at the time of study entry (unless discharge was expected within 3 days after entry into the study) [All children in Groups 1 and 2; only children £6 months of age in Group 3] Birth hospitalization >6 weeks duration or [Only children >6 months of age in Group 3] Birth hospitalization >12 weeks duration Been receiving chronic oxygen therapy or mechanical ventilation at the time of study entry (including CPAP) [Groups 1 and 2 only] Diagnosis of BPD, defined as history of prematurity and associated chronic lung disease with oxygen requirement for >28 days Congenital heart disease (CHD) (Children with medically or surgically corrected [closed] patent ductus arteriosus and no other CHD may be enrolled) Evidence of infection with hepatitis A, B, or C virus Known renal impairment, hepatic dysfunction, chronic seizure disorder, or immunodeficiency or HIV infection Mother with known HIV infection Any of the following laboratory findings in blood obtained within 7 days prior to study entry: BUN or creatinine >1.5´ the upper limit of normal for age; AST (SGOT) or ALT (SGPT) >1.5´ the upper limit of normal for age; hemoglobin <9.5 gm/dL; white blood cell count <4,000 cells/mm3; platelet count <120,000 cells/mm3 Acute illness or progressive clinical disorder Active infection, including acute RSV infection Previous reaction to IGIV, blood products, or other foreign proteins Have ever received palivizumab Received within the past 120 days or currently receiving immunoglobulin products (such as RSV-IGIV [RespiGamÒ], IVIG), or any investigational agents Currently participating in any investigational study Previously participated in any investigational study of RSV vaccines or monoclonal antibodies.

Ages Eligible for Study
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Minimum Age: 6 Months
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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>MEDI-524 | Biological: Medi-524<br>* IM doses of MEDI-524 administered at 3 mg/kg or 15 mg/kg at 30 day intervals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Describe the safety and tolerability of repeated IM doses of MEDI-524 administered at 3 mg/kg or 15 mg/kg at 30 day intervals in children at risk for serious RSV disease |  | 30 days after patient's final dose of study drug | 
| Pharmacokinetics of MEDI-524 |  | · Serum concentrations at each data collection visit will be summarized | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of MEDI-524 |  | · Serum ELISA binding activity at each data collection visit will be summarized |