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

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

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.

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.

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.