Evaluate the Safety and Efficacy of Nirsevimab in Healthy Preterm and Term Infants in China

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the Safety and Efficacy of Nirsevimab, in Healthy Preterm and Term Infants in China

Detailed Description
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This is a Phase 3 randomized, double-blind, placebo-controlled, single-dose study to determine if nirsevimab will prevent medically attended RSV-confirmed LRTI in healthy preterm and term infants entering their first RSV season. The population to be enrolled is healthy preterm and term infants > 29 weeks 0 days GA entering their first RSV season, who would not receive RSV prophylaxis based on the American Academy of Pediatrics (AAP) or other local or national guidelines. Approximately 800 subjects will be randomized 2:1 to receive a single IM dose of nirsevimab 50 mg (if weight < 5 kg) or 100 mg (if weight ≥ 5 kg) (N = 530) or placebo (N = 270). Randomization will be stratified by subject age at the time of randomization (≤ 3 months, > 3 to ≤ 6 months, > 6 months), and by GA (< 35 weeks GA, ≥ 35 weeks GA). Enrollment of infants > 6 months of age will be limited to approximately 100. All subjects will be followed through 1 year after dose administration. An independent data monitoring committee will review safety data regularly and make recommendations regarding further study conduct. Around 40 investigational study centres participate in the study.

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Nirsevimab, a Monoclonal Antibody With Extended Half-life Against Respiratory Syncytial Virus, in Healthy Preterm and Term Infants in China

Conditions
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Lower Respiratory Tract Infection

Intervention / Treatment
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* Drug: Nirsevimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Chinese preterm and term infants in their first year of life and born ≥ 29 weeks 0 days GA (infants who have an underlying illness such as cystic fibrosis or Down syndrome with no other risk factors are eligible) Infants who are entering their first RSV season at the time of screening Written informed consent and any locally required authorization 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 visits as judged by the Investigator Subject is available to complete the follow up period, which will be approximately 1 year after receipt of investigational product Exclusion Criteria: Any fever (≥ 100.4°F [≥ 38.0°C], regardless of route) or acute illness within 7 days prior to investigational product administration 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 Any drug therapy (chronic or other) within 7 days prior to randomization or expected receipt during the study with the exception of: a) multivitamins and iron; b) infrequent use of over-the-counter (OTC) medications for the systemic treatment of common childhood symptoms (eg, pain relievers) that may be permitted according to the judgment of the Investigator Any current or expected receipt of immunosuppressive agents including steroids (except for the use of topical steroids according to the judgment of the Investigator) History of receipt of blood products, or immunoglobulin products, or expected receipt through the duration of the study Hospitalization at the time of randomization, unless discharge is expected within the 7 days after randomization Known renal impairment Known hepatic dysfunction including known or suspected active or chronic hepatitis infection History of CLD/bronchopulmonary dysplasia Clinically significant congenital anomaly of the respiratory tract CHD, except for children with uncomplicated CHD (eg, patent ductus arteriosus, small septal defect) 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 or history of allergic reaction to immunoglobulin products, blood products, or other foreign proteins, 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, IV immunoglobulin) or anticipated use during the study Receipt of any investigational product Concurrent enrollment in another interventional study Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of study results 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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Accepts Healthy Volunteers

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: Nirsevimab<br>Subjects will be randomized 2:1 to receive a single IM dose of nirsevimab or placebo. | Drug: Nirsevimab<br>* Drug: injection, 100 mg/mL, a single fixed IM dose of 50 mg (if weight < 5 kg) or 100 mg (if weight ≥ 5 kg)on day 1 only.<br>* Other names: MEDI8897;|
| Placebo Comparator: Placebo<br>Subjects will be randomized 2:1 to receive a single IM dose of nirsevimab or placebo. | Drug: Placebo<br>* Commercially available 0.9% (w/v) saline (sterile for human use) fixed IM dose of 0.5 mL (if weight <5 kg) or 1.0 mL (if weight >=5 kg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of medically attended LRTI due to RT-PCR-confirmed RSV | The incidence of medically attended RSV LRTI (inpatient and outpatient) through 150 days post dose (ie, during a typical 5-month RSV season) for all infants, based on RSV test results (performed centrally using RT-PCR) and objective protocol-defined LRTI criteria, is the primary endpoint and will be presented by treatment groups. For subjects with multiple events, only the first occurrence will be used in the analysis. RSV LRTI that occurs through 150 days post dose will contribute to the primary efficacy analysis. | Day 1 to Day 151 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of RSV Hospitalization RT PCR-confirmed RSV | To assess the efficacy of nirsevimab in reducing hospitalizations due to protocol-defined LRTI caused by RT-PCR-confirmed RSV, compared to placebo | Day 1 to Day 151 | 
| Safety and tolerability | Safety and tolerability of Nirsevimab as assessed by the occurrence of all treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAE) Safety of Nirsevimab will primarily be assessed and measured by the occurrence of all treatment-emergent AEs and SAEs. Other safety assessments will include the occurrence of Adverse Event of Special Interest (AESIs) and New Onset Chronic Diseases (NOCDs). | Day 1 to Day 361 | 
| Summary of nirsevimab serum concentrations | To evaluate serum concentrations of nirsevimab. | Day 1, Day 15, Day 151 & Day 361 | 
| Incidence of ADA to nirsevimab in serum | To evaluate ADA responses to nirsevimab in serum. | Day 1, Day 151 & Day 361 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Respiratory Syncytial Viral (RSV), Efficacy, Nirsevimab, healthy Chinese preterm and term infants