Lower Respiratory Tract Infection
Conditions
Keywords
Respiratory Syncytial Viral (RSV), Efficacy, Safety, Nirsevimab, healthy Chinese preterm and term infants
Brief summary
The purpose of this study is to evaluate the Safety and Efficacy of Nirsevimab, in Healthy Preterm and Term Infants in China
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.
Interventions
DRUGNirsevimab
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.
DRUGPlacebo
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)
Sponsors
AstraZeneca
IQVIA RDS Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
0 Years to 1 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of medically attended LRTI due to RT-PCR-confirmed RSV | Day 1 to Day 151 | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of LRTI hospitalization due to 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 |
| Incidence of medically attended LRTI (protocol defined) due to RT-PCR-confirmed RSV | Day 1 to Day 151 | To assess the efficacy of nirsevimab in reducing 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) 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. |
Countries
China
Outcome results
None listed