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

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

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

Study Overview

• Status: Completed
• Conditions: Lower Respiratory Tract Infection
• Intervention / Treatment: Drug: Nirsevimab; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 800
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100191
    • Research Site
  • Changde, China, 415000
    • Research Site
  • Changsha, China, 410008
    • Research Site
  • Changsha, China, 410005
    • Research Site
  • Chengdu, China, 610041
    • Research Site
  • Chengdu, China, 610000
    • Research Site
  • Guangzhou, China, 510120
    • Research Site
  • Guangzhou, China, 510150
    • Research Site
  • Guangzhou, China, 510280
    • Research Site
  • Hangzhou, China, 310006
    • Research Site
  • Hangzhou, China, 310013
    • Research Site
  • Jiaxing, China, 314000
    • Research Site
  • Kunming, China, 650101
    • Research Site
  • Langfang, China, 065000
    • Research Site
  • Linfen, China, 041099
    • Research Site
  • Linfen, China, 41081
    • Research Site
  • Nanjing, China, 210009
    • Research Site
  • Ningbo, China, 315012
    • Research Site
  • Sanmenxia, China, 472000
    • Research Site
  • Sanya, China, 572000
    • Research Site
  • Shantou, China, 515041
    • Research Site
  • Shaoxing, China, 311800
    • Research Site
  • Shenzhen, China, 518106
    • Research Site
  • Suzhou, China, 215002
    • Research Site
  • Tangshan, China, 63003
    • Research Site
  • Tianjin, China, 300201
    • Research Site
  • Wenzhou, China, 325027
    • Research Site
  • Xinxiang, China, 453000
    • Research Site
  • Zhengzhou, China, 450018
    • Research Site
  • Zhongshan, China, 528400
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 1 year (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 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)
2. Infants who are entering their first RSV season at the time of screening
3. 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
4. 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
5. Subject is available to complete the follow up period, which will be approximately 1 year after receipt of investigational product

Exclusion Criteria:

1. Any fever (≥ 100.4°F [≥ 38.0°C], regardless of route) or acute illness within 7 days prior to investigational product administration
2. Any history of LRTI or active LRTI prior to, or at the time of, randomization
3. Known history of RSV infection or active RSV infection prior to, or at the time of, randomization
4. 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
5. Any current or expected receipt of immunosuppressive agents including steroids (except for the use of topical steroids according to the judgment of the Investigator)
6. History of receipt of blood products, or immunoglobulin products, or expected receipt through the duration of the study
7. Hospitalization at the time of randomization, unless discharge is expected within the 7 days after randomization
8. Known renal impairment
9. Known hepatic dysfunction including known or suspected active or chronic hepatitis infection
10. History of CLD/bronchopulmonary dysplasia
11. Clinically significant congenital anomaly of the respiratory tract
12. CHD, except for children with uncomplicated CHD (eg, patent ductus arteriosus, small septal defect)
13. Chronic seizure, or evolving or unstable neurologic disorder
14. Prior history of a suspected or actual acute life-threatening event
15. Known immunodeficiency, including human immunodeficiency virus (HIV)
16. Mother with HIV infection (unless the child has been proven to be not infected)
17. Any known allergy or history of allergic reaction to immunoglobulin products, blood products, or other foreign proteins, or history of allergic reaction
18. Receipt of palivizumab or other RSV mAb or any RSV vaccine, including maternal RSV vaccination
19. Receipt of any monoclonal or polyclonal antibody (for example, hepatitis B immune globulin, IV immunoglobulin) or anticipated use during the study
20. Receipt of any investigational product
21. Concurrent enrollment in another interventional study
22. Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of study results
23. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nirsevimab; Subjects will be randomized 2:1 to receive a single IM dose of nirsevimab or placebo.	Drug: Nirsevimab; 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.; Other Names: MEDI8897
Placebo Comparator: Placebo; Subjects will be randomized 2:1 to receive a single IM dose of nirsevimab or placebo.	Drug: Placebo; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of medically attended LRTI due to RT-PCR-confirmed RSV	Incidence of all medically attended LRTI (inpatient and outpatient) due to RT-PCR-confirmed RSV through 150 days after dosing (ie, during a typical 5-month RSV season)	Day 1 to Day 151

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Incidence of LRTI hospitalization due to 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
Incidence of medically attended LRTI (protocol defined) due to RT-PCR-confirmed RSV	To assess the efficacy of nirsevimab in reducing 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) 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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: IQVIA RDS Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2021
• Primary Completion (Actual): November 24, 2025
• Study Completion (Actual): November 24, 2025

Study Registration Dates

• First Submitted: October 7, 2021
• First Submitted That Met QC Criteria: November 3, 2021
• First Posted (Actual): November 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Respiratory Syncytial Viral (RSV); Nirsevimab; healthy Chinese preterm and term infants
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Respiratory Tract Infections; nirsevimab
• Other Study ID Numbers: D5290C00006; 2021-005075-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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 AZ disclosure commitment:

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

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No