Study of a Single Intramuscular Dose of Nirsevimab in the Prevention of Hospitalizations Due to Respiratory Syncytial Virus (RSV) Infection in Healthy Term and Preterm Infants During the First Year of Life

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of a single intramuscular (IM) dose of nirsevimab, compared to no intervention, for the prevention of hospitalizations due to lower respiratory tract infection (LRTI) caused by confirmed RSV infection (henceforth referred to as RSV LRTI hospitalizations) in all infants under 12 months of age who are not eligible to receive palivizumab. The visit frequency will be 1 in-person dosing/randomization visit, with monthly safety follow-up electronic contacts through the first 6 months post dosing/randomization for all participants. The study will also include a 12-month (Day 366) follow-up telephone call. The D366 follow-up telephone call will be the final follow-up telephone call for France, Germany and UK non-reconsented participants. The study will include an 18-month (D546) and a 24-month (D731, final telephone call) follow-up telephone call for UK reconsented participants.

Detailed Description
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12 months post-dosing/randomization for France, Germany and UK non-reconsented participants, 24 months post-dosing/randomization for UK reconsented participants. D01 will be the day of randomization (both study groups) and immunization (nirsevimab group).

Official Title
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A Phase IIIb Randomized Open-label Study of Nirsevimab (Versus no Intervention) in Preventing Hospitalizations Due to Respiratory Syncytial Virus in Infants (HARMONIE)

Conditions
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RSV Immunization, Healthy Volunteer

Intervention / Treatment
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* Biological: Nirsevimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Born at ≥ 29 weeks gestational age and aged 0 to 12 months (calendar age), who are entering their first RSV season on the day of inclusion in the study (D01) Informed consent form has been signed and dated by the parent(s) or other LAR(s) (and by an independent witness if required by local regulations) Participant and parent/LAR are able to attend the scheduled visit and to comply with all study procedures Exclusion Criteria: Participants are not eligible for the study if any of the following criteria are met: Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) Active confirmed RSV infection at the time of dosing/randomization Active LRTI at the time of dosing/randomization Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study intervention used in the study or to a product containing any of the same substances Laboratory confirmed thrombocytopenia, or known thrombocytopenia, as reported by the parent/LAR, contraindicating intramuscular injection Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular injection Any condition that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on the day of study intervention administration. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided Mother of the infant participant was administered an RSV vaccine during her pregnancy with the infant participant Receipt of any monoclonal antibody by the infant participant Receipt of immune globulins, blood or blood-derived products in the past 3 months by the infant participant Participation at the time of study enrollment or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure Eligible to receive palivizumab at time of inclusion (as per local guidelines) In an emergency setting or hospitalized involuntarily Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1 in-person randomization visit, with monthly safety and efficacy follow-up conducted through electronic contact through the first 6 months post-dosing/randomization. The study will also include a 12-month (D366) follow-up telephone call. The D366 follow-up telephone call will be the final follow-up telephone call for France, Germany and UK non-reconsented participants. The study will include an 18-month (D546) and a 24-month (D731, final telephone call) follow-up telephone call for UK reconsented participants.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nirsevimab<br>1 intramuscular injection at Day 01 | Biological: Nirsevimab<br>* Pharmaceutical Form: Solution for Injection Route of Administration: Intramuscular<br>|
| No Intervention: No preventive intervention for RSV<br>No intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall incidence of RSV LRTI hospitalization through the RSV season | Number of RSV LRTI hospitalization through the RSV season. | Up to 180 days post-dosing/randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of very severe RSV LRTI through the RSV season | Number of very severe RSV LRTI through the RSV season. Severe RSV LRTI are defined as confirmed RSV hospitalization for LRTI with an oxygen saturation (SaO2) < 90% (at any time) and oxygen supplementation. | Up to 180 days post-dosing/randomization | 
| Incidence of hospitalization for LRTI through the RSV season in each country | Number of RSV LRTI hospitalization in each country through the RSV season. | Up to 180 days post-dosing/randomization | 
| Overall hospitalization for allcause LRTI in all 3 countries combined throughout the RSV season | Number of RSV LRTI hospitalization in all 3 countries combined through the RSV season. | Up to 180 days post-dosing/randomization | 
| Incidence (overall and in each country) of RSV LRTI hospitalization throughout 150 days post-dosing/randomization | Number of RSV LRTI hospitalization, overall and in each country, throughout 150 days post-dosing/randomization. | Day 151 | 
| Incidence of very severe RSV LRTI in all 3 countries combined through 150 days post-dosing/randomization | Number of very severe RSV LRTI in all 3 countries combined through 151 days post-dosing/randomization. Severe RSV LRTI are defined as confirmed RSV hospitalization for LRTI with an oxygen saturation (SaO2) < 90% (at any time) and oxygen supplementation. | Day 151 | 
| Incidence of hospitalizations for all cause LRTI through 150 days post-dosing/randomization | Number of hospitalizations for all cause LRTI through 150 days post-dosing/randomization | Day 151 | 
| Incidence of RSV LRTI hospitalization throughout the second year post-immunization/randomization | Number of RSV LRTI hospitalizations | Day 366 to Day 731 | 
| Incidence of hospitalizations for all-cause LRTI throughout the second year post immunization/randomization | Number of hospitalizations for all-cause LRTI | Day 366 to Day 731 | 
| Any immediate adverse events (AEs) reported in the 30◦minutes after immunization | Number of participants experiencing immediate AEs | 30 minutes after immunization | 
| Non-serious AEs from D01 (post-dosing/randomization) to D31 | Number of non-serious AEs | Day 01 to Day 31 | 
| Adverse events of special interest (AESIs) from D01 visit through 1-year post-dosing/randomization or D366 | Number of participants experiencing AESIs | Day 01 through 1-year post-dosing/randomization (Day 366) | 
| Medically attended adverse events (MAAEs) from D01 visit through 1-year post-dosing/randomization or D366 | Number of participants experiencing MAAEs | Day 01 through 1-year post-dosing/randomization (Day 366) | 
| Serious adverse events (SAEs) from D01 visit through 1-year post-dosing/randomization or D366 | Number of participants experiencing SAEs | Day 01 through 1-year post-dosing/randomization (Day 366) | 
| Related SAEs from D366 to D731 for United Kingdom (UK) participants | Number of UK participants experiencing SAEs related to study intervention | Day 366 to D 731 | 
| Incidence of RSV LRTI hospitalizations through 180 days post-dosing/randomization (overall and in each country) | Number of RSV LRTI hospitalizations overall and in each country | Day 01 through 180 days post-dosing/randomization | 
| Incidence of hospitalizations for all cause LRTI through 180 days post-dosing/randomization | Number of hospitalizations for all-cause LRTI | Day 01 through 180 days post-dosing/randomization | 
| Incidence of RSV LRTI hospitalization from 181 days post-dosing/randomization until D366 the end of the study (overall and in each country) | Number of RSV LRTI hospitalizations overall and in each country | 181 days post-dosing/randomization until Day 366 | 
| Incidence of hospitalizations for all cause LRTI from 181 days post-dosing/randomization until D366 | Number of hospitalizations for all-cause LRTI | 181 days post-dosing/randomization until Day 366 | 
| Incidence of recurrent wheeze in UK reconsented participants from D01 to D731 | Number of UK reconsented participants with recurrent wheeze | Day 01 to Day 731 |