Evaluate the Safety and Tolerability, for Nirsevimab in Immunocompromised Children

NCT ID: NCT04484935

Last Updated: 2023-11-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-19
• Study Completion Date: 2023-02-17

Brief Summary

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

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.

Conditions

RSV Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Nirsevimab

1st RSV season: 50mg nirsevimab

1. st RSV season: 100mg nirsevimab

2. nd RSV season: 200mg nirsevimab

Group Type: EXPERIMENTAL

Nirsevimab

Intervention Type: DRUG

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

Interventions

Nirsevimab

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

Intervention Type: DRUG

Other Intervention Names

Nirsevimab (MEDI8897)

Eligibility Criteria

Inclusion Criteria

• Neonate, infant, or young child ≤ 24 months of age at the time of dose administration who, per investigator judgement, are:

1. In their first year of life AND entering their first RSV season at the time of dose administration OR

2. 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.

1. 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

2. Diagnosed with human immunodeficiency virus infection, or

3. History of organ or bone marrow transplantation, or

4. Subject is receiving immunosuppressive chemotherapy, or

5. Subject is receiving systemic high-dose corticosteroid therapy (prednisone equivalents ≥ 0.5 mg/kg every other day, other than inhaler or topical use), or

6. 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.

1. Subject born at ≤ 28 weeks gestation and is ≤ 12 months of age

2. Subject born at 29 to 35 weeks gestation and is ≤ 6 months of age

3. Age ≤ 24 months with a history of bronchopulmonary dysplasia requiring medical management within the past 6 months

4. Age ≤ 24 months with current hemodynamically significant congenital heart disease (CHD)

5. 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.

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iqvia Pty Ltd

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Los Angeles, California, United States

Research Site

Tampa, Florida, United States

Research Site

Syracuse, New York, United States

Research Site

North Charleston, South Carolina, United States

Research Site

Memphis, Tennessee, United States

Research Site

Fort Worth, Texas, United States

Research Site

Tacoma, Washington, United States

Research Site

Brussels, , Belgium

Research Site

Liège, , Belgium

Research Site

Bunkyō City, , Japan

Research Site

Fuchu-shi, , Japan

Research Site

Kawasaki-shi, , Japan

Research Site

Kurume-shi, , Japan

Research Site

Kyoto, , Japan

Research Site

Nagasaki, , Japan

Research Site

Setagaya-ku, , Japan

Research Site

Tsukuba, , Japan

Research Site

Yokohama, , Japan

Research Site

Bydgoszcz, , Poland

Research Site

Parktown, , South Africa

Research Site

Soweto, , South Africa

Research Site

Barcelona, , Spain

Research Site

Granada, , Spain

Research Site

Madrid, , Spain

Research Site

Madrid, , Spain

Research Site

Dnipro, , Ukraine

Research Site

Kharkiv, , Ukraine

Research Site

Nottingham, , United Kingdom

Countries

United States; Belgium; Japan; Poland; South Africa; Spain; Ukraine; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D5290C00008&amp;attachmentIdentifier=e1f614d0-cc7a-48b9-bd02-b07ef3f57993&amp;fileName=D5290C00008_(MUSIC)_CSR_synopsis_Redacted_PDFA.pdf&amp;versionIdentifier=

CSRsynopsis

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D5290C00008&amp;attachmentIdentifier=f452db79-fd73-45bd-9478-ced954a3eb54&amp;fileName=D5290C00008_(MUSIC)_CSP_V3_Redacted_PDFA.pdf&amp;versionIdentifier=

CSP

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SAP

Other Identifiers

2021-003221-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D5290C00008

Identifier Type: -

Identifier Source: org_study_id