Evaluate the Safety and Tolerability, for Nirsevimab in Immunocompromised Children (MUSIC)

• ClinicalTrials.gov Identifier: NCT04484935
• Recruitment Status: Active, not recruiting
• First Posted: July 24, 2020
• Last Update Posted: November 14, 2022
• Sponsor: AstraZeneca
• Collaborator: Iqvia Pty Ltd
• Information provided by (Responsible Party): AstraZeneca

Study Description

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.

Condition or disease	Intervention/treatment	Phase
RSV Infection	Drug: Nirsevimab	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Open: no masking is used. All involved know the identity of the intervention assignment.
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: August 19, 2020
• Estimated Primary Completion Date: February 23, 2023
• Estimated Study Completion Date: February 23, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nirsevimab; 1st RSV season: 50mg nirsevimab; st RSV season: 100mg nirsevimab; nd RSV season: 200mg nirsevimab	Drug: 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; Other Name: Nirsevimab (MEDI8897)

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability of nirsevimab when administered to immunocompromised children ≤ 24 months of age [ Time Frame: Through 360 days post dose. ]
   All treatment-emergent adverse event (TEAEs), treatment-emergent serious adverse event (TESAEs), adverse event of special interest (AESIs), new onset chronic disease (NOCDs)

Secondary Outcome Measures :

1. To evaluate the PK of nirsevimab [ Time Frame: Through 360 days post dose. ]
   Summary of nirsevimab serum concentrations
2. To evaluate ADA responses to nirsevimab in serum [ Time Frame: Through 360 days post dose. ]
   Incidence of ADA to nirsevimab in serum
3. To assess the efficacy of nirsevimab when administered as a single intramuscular (IM) dose to infants ≤ 24 months of age [ Time Frame: Through 360 days post dose ]
   Incidence of medically attended lower respiratory tract infection (LRTI; inpatient and outpatient) and hospitalizations due to reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed respiratory syncytial virus (RSV) through 150 days after administration of nirsevimab

Eligibility Criteria

• Ages Eligible for Study: 0 Years to 2 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

Research Site

Los Angeles, California, United States, 90027

United States, Florida

Research Site

Tampa, Florida, United States, 33606

United States, New York

Research Site

Syracuse, New York, United States, 13210

United States, South Carolina

Research Site

North Charleston, South Carolina, United States, 29406

United States, Tennessee

Research Site

Memphis, Tennessee, United States, 38105

United States, Texas

Research Site

Fort Worth, Texas, United States, 76104

United States, Washington

Research Site

Tacoma, Washington, United States, 98405

Belgium

Research Site

Bruxelles, Belgium, 1200

Research Site

Liège, Belgium, 4000

Japan

Research Site

Bunkyo-ku, Japan, 113-8519

Research Site

Fuchu-shi, Japan, 183-8561

Research Site

Kawasaki-shi, Japan, 216-8511

Research Site

Kurume-shi, Japan, 830-0011

Research Site

Kyoto-shi, Japan, 606-8507

Research Site

Nagasaki-shi, Japan, 852-8501

Research Site

Setagaya-ku, Japan, 157-8535

Research Site

Tsukuba-shi, Japan, 305-8576

Research Site

Yokohama-shi, Japan, 232 8555

Poland

Research Site

Bydgoszcz, Poland, 85-048

South Africa

Research Site

Parktown, South Africa, 2193

Research Site

Soweto, South Africa, 2013

Spain

Research Site

Barcelona, Spain, 8035

Research Site

Granada, Spain, 18014

Research Site

Madrid, Spain, 28041

Research Site

Madrid, Spain, 28046

Ukraine

Research Site

Dnipro, Ukraine, 49006

Research Site

Kharkiv, Ukraine, 61075

United Kingdom

Research Site

Nottingham, United Kingdom, NG7 2UH

Sponsors and Collaborators

AstraZeneca

Iqvia Pty Ltd

More Information

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT04484935
• Other Study ID Numbers: D5290C00008
• First Posted: July 24, 2020
• Last Update Posted: November 14, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AstraZeneca (AZ) disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AstraZeneca (AZ) are accepting requests for Individual Participant Data (IPD), but this does not mean all requests will be shared.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the European Federation of Pharmaceutical Industries and Associations (EFPIA) Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:

LRTI by RSV infection

Additional relevant MeSH terms:

Respiratory Syncytial Virus Infections; Infections; Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases