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

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05110261

Collaborator

IQVIA RDS (Shanghai) Co., Ltd. (Other)

800

Enrollment

Locations

Arms

48.8

Anticipated Duration (Months)

22.2

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Lower Respiratory Tract Infection	Drug: Nirsevimab Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

800 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Nov 24, 2021

Anticipated Primary Completion Date :

May 23, 2025

Anticipated Study Completion Date :

Dec 19, 2025

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

Incidence of medically attended LRTI due to RT-PCR-confirmed RSV [Day 1 to Day 151]
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.

Secondary Outcome Measures

Incidence of RSV Hospitalization RT PCR-confirmed RSV [Day 1 to Day 151]
To assess the efficacy of nirsevimab in reducing hospitalizations due to protocol-defined LRTI caused by RT-PCR-confirmed RSV, compared to placebo
Safety and tolerability [Day 1 to Day 361]
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).
Summary of nirsevimab serum concentrations [Day 1, Day 15, Day 151 & Day 361]
To evaluate serum concentrations of nirsevimab.
Incidence of ADA to nirsevimab in serum [Day 1, Day 151 & Day 361]
To evaluate ADA responses to nirsevimab in serum.

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 1 Year

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Research Site	Beijing	China	100191
2	Research Site	Changde	China	415003
3	Research Site	Changsha	China	410005
4	Research Site	Changsha	China	410008
5	Research Site	Changsha	China	410008
6	Research Site	Chengdu	China	610000
7	Research Site	Chengdu	China	610041
8	Research Site	Guangzhou	China	510120
9	Research Site	Guangzhou	China	510150
10	Research Site	Guangzhou	China	510280
11	Research Site	Hangzhou	China	310006
12	Research Site	Hangzhou	China	310013
13	Research Site	Jiaxing	China	314000
14	Research Site	Kunming	China	650101
15	Research Site	Langfang	China
16	Research Site	Linfen	China	041099
17	Research Site	Linfen	China	41081
18	Research Site	Nanjing	China	210009
19	Research Site	Ningbo	China	315012
20	Research Site	Sanmenxia	China	472000
21	Research Site	Sanya City	China	572000
22	Research Site	Shantou	China	515041
23	Research Site	Shaoxing	China	311800
24	Research Site	Shenzhen	China	518053
25	Research Site	Shenzhen	China	518106
26	Research Site	Suzhou	China	215002
27	Research Site	Tangshan	China	63003
28	Research Site	Tianjin	China	300074
29	Research Site	Tianjin	China	300201
30	Research Site	Tonghua	China	134000
31	Research Site	Wenzhou	China	325027
32	Research Site	Wuxi	China	214023
33	Research Site	Xiamen	China	361003
34	Research Site	Xinxiang	China	453000
35	Research Site	Zhengzhou	China	450018
36	Research Site	Zhongshan	China	528400