A Study to Evaluate the Safety of MEDI8897 for the Prevention of Medically Attended Respiratory Syncytial Virus(RSV) Lower Respiratory Track Infection (LRTI) in High-risk Children

This study is a pivotal Phase 2/3 randomized, double-blind, palivizumab-controlled study to evaluate the safety, pharmacokinetics (PK), anti-drug antibody (ADA) response, and descriptive efficacy for MEDI8897 in high-risk infants eligible to receive palivizumab when entering their first or second RSV season (Season 1 or Season 2, respectively). Approximately 900 palivizumab-eligible infants entering their first RSV season will be enrolled into one of 2 cohorts: (1) preterm cohort, including approximately 600 preterm infants (≤ 35 weeks gestational age [GA]) without CLD/CHD, or (2) CLD/CHD cohort, including approximately 300 infants with CLD of prematurity or hemodynamically significant CHD. A minimum of 100 infants with hemodynamically significant CHD will be enrolled. Within each cohort, randomization will be stratified by hemisphere (northern, southern) and subject age at the time of Season 1 randomization (≤ 3 months, > 3 to ≤ 6 months, > 6 months).

Inclusion criteria

• For the preterm cohort (excluding subjects with CLD or hemodynamically significant CHD): preterm infants in their first year of life and born ≤ 35 weeks 0 days GA eligible to receive palivizumab in accordance with national or local guidelines, including those with:

• Uncomplicated small atrial or ventricular septal defects or patent ductus arteriosus, or
• Aortic stenosis, pulmonic stenosis, or coarctation of the aorta alone
• For the CLD/CHD cohort:

• Subjects with CLD - infants in their first year of life and a diagnosis of CLD of prematurity requiring medical intervention/management (ie, supplemental oxygen, bronchodilators, or diuretics) within the 6 months prior to randomization
• Subjects with CHD - infants in their first year of life and documented, hemodynamically significant CHD (must be unoperated or partially corrected CHD) Note: Infants with hemodynamically significant acyanotic cardiac lesions must have pulmonary hypertension (≥ 40 mmHg measured pressure in the pulmonary artery) or the need for daily medication to manage CHD
• Infants who are entering their first RSV season at the time of screening
• Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the USA, EU Data Privacy Directive in the EU) obtained from the subject's parent(s)/legal representative(s) prior to performing any protocol-related procedures, including screening evaluations
• Subject's parent(s)/legal representative(s) able to understand and comply with the requirements of the protocol including follow-up and illness visits as judged by the investigator
• Subject is available to complete the follow-up period, which will be 1 year after Season 1/ Dose 1 for subjects without CLD/CHD, or 1 year after Season 2/Dose 1 (or last replacement dose as applicable for CHD) for subjects with CLD/CHD

Exclusion criteria

• Any fever (≥ 100.4°F [≥ 38.0°C], regardless of route) or acute illness within 7 days prior to randomization
• Any history of LRTI or active LRTI prior to, or at the time of, randomization
• Known history of RSV infection or active RSV infection prior to, or at the time of, randomization
• Hospitalization at the time of randomization, unless discharge is expected within the 7 days after randomization
• Requirement for mechanical ventilation, extracorporeal membrane oxygenation, CPAP, or other mechanical respiratory or cardiac support at the time of randomization
• Anticipated cardiac surgery within 2 weeks after randomization
• Anticipated survival of < 6 months after randomization
• Receipt of any investigational drug
• Known renal impairment
• Known hepatic dysfunction including known or suspected active or chronic hepatitis infection
• Clinically significant congenital anomaly of the respiratory tract
• Chronic seizure, or evolving or unstable neurologic disorder
• Prior history of a suspected or actual acute life-threatening event
• Known immunodeficiency, including human immunodeficiency virus (HIV)
• Mother with HIV infection (unless the child has been proven to be not infected)
• Any known allergy, including to immunoglobulin products, or history of allergic reaction
• Receipt of palivizumab or other RSV mAb or any RSV vaccine, including maternal RSV vaccination
• Receipt of any monoclonal or polyclonal antibody (for example, hepatitis B immune globulin, intravenous immunoglobulin) or anticipated use during the study
• Any condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of subject safety or study results
• Concurrent enrollment in another interventional study
• Children of employees of the sponsor, clinical study site, or any other individuals involved with the conduct of the study, or immediate family members of such individuals