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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of MEDI8897 compared to palivizumab when administered to preterm infants entering their first RSV season and children with chronic lung disease (CLD) and congenital heart disease (CHD) entering their first and second RSV season.

Detailed Description
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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).

Official Title
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A Phase 2/3 Randomized, Double-blind, Palivizumab-controlled Study to Evaluate the Safety of MEDI8897, a Monoclonal Antibody With an Extended Half-life Against Respiratory Syncytial Virus, in High-risk Children (MEDLEY)

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Drug: MEDI8897
* Drug: Palivizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 1 Year

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: MEDI8897<br>anti-RSV monoclonal antibody with an extended half-life | Drug: MEDI8897<br>* Anti-RSV monoclonal antibody with an extended half-life<br>|
| Active Comparator: Palivizumab<br>anti-RSV monoclonal antibody | Drug: Palivizumab<br>* Approved anti-RSV monoclonal antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of MEDI8897 as Assessed by the Occurrence of All Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) and New Onset Chronic Disease (NOCD) | Safety and tolerability of MEDI8897 will be assessed by the occurrence of all treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs) , adverse events of special interest (AESIs), and new onset chronic diseases (NOCDs) | 360 days post first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentrations of MEDI8897 and Palivizumab | Summary of individual MEDI8897 and palivizumab serum concentration data by treatment group along with descriptive statistics. | Day 15, Day 31, Day 151 post first dose in Season 1 and Season 2 | 
| Incidence of Anti-drug Antibody (ADA) to MEDI8897 and Palivizumab in Serum | Incidence of ADA to MEDI8897 and palivizumab as assessed by the percentage of participants with any post-baseline ADA positive by treatment group. | 360 days post first dose | 
| Incidence of Medically Attended Lower Respiratory Track Infection (LRTI) and Hospitalization Due to Reverse Transcriptase Chain Reaction (RT-PCR) Confirmed Respiratory Syncytial Virus (RSV) Through 150 Days Post First Dose | Incidence of medically attended LRTI (inpatient and outpatient) due to RT-PCR-confirmed RSV through 150 days after Dose 1 for season 1 and season 2. Incidence of LRTI hospitalizations due to RT-PCR-confirmed RSV through 150 days after Dose 1 for season 1 and season 2. | 150 days post first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory Syncytial Virus Infections, Preterm Infants, Lower Respiratory Infection