Evaluate the Safety and Tolerability, for Nirsevimab in Immunocompromised Children

Study Overview
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Brief Summary
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Study D5290C00008 is a Phase 2, open-label, uncontrolled, single-dose study to evaluate the safety and tolerability, pharmacokinetic(s) (PK), occurrence of antidrug antibody (ADA), and efficacy of nirsevimab in immunocompromised children who are ≤ 24 months of age at the time of dose administration. Approximately 100 subjects will be enrolled. Subjects will be followed for approximately 1 year after dose administration.

Detailed Description
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Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) among infants and young children, resulting in annual epidemics in Japan. Children with congenital or acquired immunodeficiencies, transplant recipients, and those receiving immunosuppressive therapy are at increased risk for severe RSV-associated LRTI with prolonged viral shedding and higher viral loads, resulting in prolonged hospitalizations, admissions to the intensive care unit (ICU), and the need for mechanical ventilation. Palivizumab (Synagis®) is the only approved agent for RSV prophylaxis, and its half-life (t1/2) is approximately 1 month, infants and young children need to receive monthly intramuscular doses of palivizumab throughout the RSV season to maintain protection. This constitutes a significant burden on healthcare providers as well as the infants/children and their families. Nirsevimab may provide a cost-effective opportunity to protect all infants from RSV disease based on an improvement in potency and the extended t1/2 that is expected to support once-per-RSV-season dosing.

Official Title
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A Phase 2, Open-label, Uncontrolled, Single-dose Study to Evaluate the Safety and Tolerability, Pharmacokinetics, and Occurrence of Antidrug Antibody for Nirsevimab in Immunocompromised Children ≤ 24 Months of Age

Conditions
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RSV Infection

Intervention / Treatment
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* Drug: Nirsevimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neonate, infant, or young child ≤ 24 months of age at the time of dose administration who, per investigator judgement, are: In their first year of life AND entering their first RSV season at the time of dose administration OR In their second year of life AND entering their second RSV season at the time of dose administration The subject must meet at least 1 of the following conditions at the time of informed consent. Diagnosed with combined immunodeficiency (severe combined immunodeficiency, X-linked hyper-immunoglobulin M [IgM] syndrome, etc); antibody deficiency (X linked agammaglobulinemia, common variable immunodeficiency, non-X-linked hyper-IgM syndromes, etc); or other immunodeficiency (Wiskott-Aldrich syndrome, DiGeorge syndrome, etc), or Diagnosed with human immunodeficiency virus infection, or History of organ or bone marrow transplantation, or Subject is receiving immunosuppressive chemotherapy, or Subject is receiving systemic high-dose corticosteroid therapy (prednisone equivalents ≥ 0.5 mg/kg every other day, other than inhaler or topical use), or Subject is receiving other immunosuppressive therapy (eg, azathioprine, methotrexate, mizoribine, mycophenolate mofetil, cyclophosphamide, cyclosporine, tacrolimus, cytokine inhibitors, etc) 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 nirsevimab Exclusion Criteria: Subject who meets any of the palivizumab indications approved in Japan other than immunocompromised condition. Subject born at ≤ 28 weeks gestation and is ≤ 12 months of age Subject born at 29 to 35 weeks gestation and is ≤ 6 months of age Age ≤ 24 months with a history of bronchopulmonary dysplasia requiring medical management within the past 6 months Age ≤ 24 months with current hemodynamically significant congenital heart disease (CHD) Age ≤ 24 months with Down syndrome Requirement for oxygen supplementation, mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure, or other mechanical respiratory or cardiac support at screening A current, active infection, including RSV infection, at the time of screening or at the time of investigational product administration. Any fever (≥ 100.4°F [≥ 38.0°C], regardless of route) or acute illness within 7 days prior to investigational product administration. Any serious concurrent medical condition (renal failure, hepatic dysfunction, suspected active or chronic hepatitis infection, seizure disorder, unstable neurologic disorder, etc), except those resulting in an immune deficiency condition. Clinically significant congenital anomaly of the respiratory tract. Receipt of palivizumab. Any known allergy or history of allergic reaction to any component of nirsevimab. Any known allergy or history of allergic reaction to immunoglobulin products, blood products, or other foreign proteins. Concurrent enrollment in another interventional study, or prior receipt of any investigational agent. Anticipated survival of less than 1 year at the time of informed consent. 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: 2 Years

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nirsevimab<br>1st RSV season: 50mg nirsevimab st RSV season: 100mg nirsevimab nd RSV season: 200mg nirsevimab | Drug: Nirsevimab<br>* Single fixed IM dose of nirsevimab 50 mg if body weight < 5 kg or 100 mg if body weight ≥ 5 kg, and subjects entering their second RSV season will receive a single fixed IM dose of nirsevimab 200 mg<br>* Other names: Nirsevimab (MEDI8897);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs (TESAEs), AEs of Special Interest (AESIs), and New Onset Chronic Disease (NOCDs) | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the treatment. TEAEs were AEs whose onset occurred after receiving nirsevimab and within 360 days post dose. A TESAE was any AE that resulted in death, was life-threatening, required inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality, or was medically significant. AESIs were defined as AEs of immediate (type I) hypersensitivity (including anaphylaxis), thrombocytopenia, and immune complex disease following the administration of nirsevimab based on investigator assessment and Medical Dictionary for Regulatory Activities (MedDRA) preferred term (PT) codes. An NOCD was a newly diagnosed medical condition of a chronic, ongoing nature post administration of treatment. | TEAEs were collected from the first dose administration (Day 1) up to 360 days post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentrations of Nirsevimab | Serum concentrations of nirsevimab at selected time points were evaluated to confirm that adequate exposures for protection from respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) are maintained for at least 5 months after dosing. | Baseline (Day 1) and on Days 8 (for Japanese participants), 31, 151 and 361 | 
| Number of Participants With Anti-Drug Antibody (ADA) Response to Nirsevimab | Blood samples were analyzed for the presence of ADAs for nirsevimab using validated assays. | Baseline (Day 1) and on Days 31, 151 and 361 | 
| Number of Participants With Medically Attended (MA) RSV LRTI (Inpatient and Outpatient) and Hospitalizations | Number of participants with LRTI and hospitalizations due to reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed RSV was assessed. MA RSV LRTI consisted of participants with protocol-defined LRTI, positive central RT-PCR RSV test result, Investigator assessed LRTI at an inpatient or outpatient setting. MA RSV LRTI with hospitalization consisted of participants with protocol-defined LRTI, positive central RT-PCR RSV test result, Investigator assessed LRTI at an inpatient setting. | Through 150 days post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LRTI by RSV infection