Healthy Volunteer, RSV Immunization
Conditions
Brief summary
The purpose of this study was 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 were not eligible to receive palivizumab. The visit frequency was 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 also included a 12-month (Day 366) follow-up telephone call. The D366 follow-up telephone call was the final follow-up telephone call for France, Germany and UK non-reconsented participants. The study included an 18-month (D546) and a 24-month (D731, final telephone call) follow-up telephone call for UK reconsented participants.
Detailed description
12 months post-dosing/randomization for France, Germany and UK non-reconsented participants, 24 months post-dosing/randomization for UK reconsented participants. D01 was the day of randomization (both study groups) and immunization (nirsevimab group).
Interventions
BIOLOGICALNirsevimab
Pharmaceutical Form: Solution for Injection Route of Administration: Intramuscular
Sponsors
AstraZeneca
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention 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 also included a 12-month (D366) follow-up telephone call. The D366 follow-up telephone call was the final follow-up telephone call for France, Germany and UK non-reconsented participants. The study included an 18-month (D546) and a 24-month (D731, final telephone call) follow-up telephone call for UK reconsented participants.
Eligibility
Sex/Gender
ALL
Age
0 Days to 12 Months
Healthy volunteers
Yes
Inclusion criteria
* Born at ≥ 29 weeks gestational age and aged 0 to 12 months (calendar age), who entered their first RSV season on the day of inclusion in the study (D01) * Informed consent form was 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 were able to attend the scheduled visit and to comply with all study procedures
Exclusion criteria
* Participants were 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 was not 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 were not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI) Hospitalization Through the Respiratory Syncytial Virus Season | From dosing/randomization (Day 1) up to approximately 7 months | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths per minute (/min); 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. RSV season was the period of increased RSV infection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season | From dosing/randomization (Day 1) up to approximately 7 months | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Very severe RSV LRTI was defined as RSV LRTI hospitalization with oxygen saturation \<90% (at any time during hospitalization) and oxygen supplementation. Hospitalization was defined as the decision to admit to in-patient care by the treating physician. RSV season was the period of increased RSV infection. |
| Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through the Respiratory Syncytial Virus Season in Each Country | From dosing/randomization (Day 1) up to approximately 7 months | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. RSV season was the period of increased RSV infection. Number of participants with RSV LRTI hospitalization through the RSV season in France, UK, and Germany is presented. |
| Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season | From dosing/randomization (Day 1) up to approximately 7 months | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. RSV season was the period of increased RSV infection. Number of participants with hospitalization for all-cause LRTI through the RSV season in France, UK, Germany, and overall is presented. |
| Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | From dosing/randomization (Day 1) to Day 151 | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Very severe RSV LRTI was defined as RSV LRTI hospitalization with oxygen saturation \<90% (at any time during hospitalization) and oxygen supplementation. Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with very severe RSV LRTI through 151 days post-dosing/randomization in France, UK, Germany, and overall is presented. |
| Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | From dosing/randomization (Day 1) to Day 151 | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with hospitalization for all-cause LRTI through 151 days post-dosing/randomization in France, UK, Germany, and overall is presented. |
| Number of Participants With Immediate Treatment-Emergent Adverse Events (TEAEs) | Up to 30 minutes post-dosing/randomization on Day 1 | An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were either events with the start date and time posterior to the start of the treatment period and up to the end of the treatment period or events with the start date and time prior to the start of the treatment period, whose severity was greater than 1 or missing and stop date is missing or not before the treatment period. Immediate events were recorded to capture medically relevant AEs which occurred within the first 30 minutes after immunization. |
| Number of Participants With Non-Serious Treatment-Emergent Adverse Events | From dosing/randomization (Day 1) to Day 31 | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were either events with the start date and time posterior to the start of the treatment period and up to the end of the treatment period or events with the start date and time prior to the start of the treatment period, whose severity was greater than 1 or missing and stop date was missing or not before the treatment period. |
| Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events of Special Interest (AESIs) and Treatment-Emergent Medically Attended Adverse Events (MAAEs) | From dosing/randomization (Day 1) to Day 366 | AE: untoward medical occurrence in clinical study participant, temporally associated with use of study intervention, whether or not related to it. TEAEs: events with start date/time posterior to start of treatment period(TP) and up to end of TP, or events with start date/time prior to start of TP, whose severity was\>1/missing; stop date was missing/not before TP. SAE: AE at any dose resulting in death, persistent or significant disability/incapacity, required inpatient hospitalization/prolongation of existing hospitalization, was life-threatening or congenital anomaly/birth defect or medically important event. MAAE: new onset/worsening of condition that prompted participant or participant's parent/legally acceptable representative to seek unplanned medical advice at physician's office/Emergency Department. AESI: scientific, medical concern specific to Sponsor's study intervention/program for which ongoing monitoring and rapid communication by investigator to Sponsor was appropriate. |
| Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 151 Days Post-dosing/Randomization | From dosing/randomization (Day 1) to Day 151 | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with RSV LRTI hospitalization through 151 days post-dosing/randomization in France, UK, Germany, and overall is presented. |
| Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 181 Days Post-dosing/Randomization | From dosing/randomization (Day 1) to Day 181 | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with RSV LRTI hospitalization through 181 days post-dosing/randomization in France, UK, Germany, and overall is presented. |
| Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 181 Days Post-dosing/Randomization | From dosing/randomization (Day 1) to Day 181 | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with hospitalization for all-cause LRTI through 181 days post-dosing/randomization in France, UK, Germany, and overall is presented. |
| Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 181 to 366 Post-dosing/Randomization | From Day 181 to Day 366 | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with RSV LRTI hospitalization from Days 181 to 366 post-dosing/randomization (with no RSV LRTI hospitalizations before Day 181) in France, UK, Germany, and overall is presented. |
| Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection From Days 181 to 366 Post-dosing/Randomization | From Day 181 to Day 366 | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with hospitalization for all-cause LRTI from Days 181 to 366 post-dosing/randomization (with no hospitalizations for all-cause LRTI before Day 181) is presented. |
| Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 366 to 731 Post-dosing/Randomization (for United Kingdom Reconsented Participants) | From Day 366 to Day 731 | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with RSV LRTI hospitalization from Days 366 to 731 post-dosing/randomization (with no RSV LRTI hospitalizations before Day 366) in UK reconsented participants is presented. |
| Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection From Days 366 to 731 Post-dosing/Randomization (for United Kingdom Reconsented Participants) | From Day 366 to Day 731 | LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with hospitalization for all-cause LRTI from Days 366 to 731 post-dosing/randomization (with no hospitalizations for all-cause LRTI before Day 366) in UK reconsented participants is presented. |
| Number of Participants With Recurrent Wheeze (for United Kingdom Reconsented Participants) | From dosing/randomization (Day 1) to Day 731 | Wheeze was defined as a physician-diagnosed wheeze or asthma or related ear, nose and throat (ENT)/respiratory symptoms at an office visit or an illness for which the child was prescribed medication to treat an ENT/respiratory condition. Recurrent wheeze event was defined as 2 or more protocol-defined wheeze episodes throughout follow-up period. |
| Number of Participants With Treatment-Related Serious Adverse Event (for United Kingdom Reconsented Participants) | From Day 366 to Day 731 | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were either events with the start date and time posterior to the start of the treatment period and up to the end of the treatment period or events with the start date and time prior to the start of the treatment period, whose severity was greater than 1 or missing and stop date is missing or not before the treatment period. SAE: AE at any dose resulting in death, persistent or significant disability/incapacity, required inpatient hospitalization/prolongation of existing hospitalization, was life-threatening or congenital anomaly/birth defect or medically important event. A treatment-related TEAE was a TEAE considered by the investigator as related or with unknown/missing relationship to treatment for participants who received nirsevimab on Day 1. |
Countries
France, Germany, United Kingdom
Participant flow
Recruitment details
The study was conducted at 235 investigational sites in France, Germany and the United Kingdom (UK).
Pre-assignment details
Total 8057 participants were enrolled and randomized in 1:1 ratio to nirsevimab or no intervention group between 08 August 2022 to 28 February 2023. Participants were followed up for safety for 12-months (366 days) (for France, Germany, and UK non-reconsented participants) and for 24 months (731 days) (for UK participants who consented to take part into study extension \[UK reconsented participants\]). As pre-specified in protocol and SAP, results are presented by treatment group.
Participants by arm
| Arm | Count |
|---|---|
| Nirsevimab Participants received nirsevimab 50 mg (if weight \<5 kg) or 100 mg (if weight ≥5 kg) as a single IM injection on Day 1. | 4,038 |
| No Intervention Participants received no RSV preventive intervention on Day 1. | 4,019 |
| Total | 8,057 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lost to Follow-up | 265 | 358 |
| Overall Study | Protocol Deviation | 1 | 6 |
| Overall Study | Withdrawal by Parent/Guardian | 23 | 23 |
Baseline characteristics
| Characteristic | Nirsevimab | No Intervention | Total |
|---|---|---|---|
| Age, Continuous | 4.53 months STANDARD_DEVIATION 3.342 | 4.48 months STANDARD_DEVIATION 3.294 | 4.51 months STANDARD_DEVIATION 3.318 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 1950 Participants | 1912 Participants | 3862 Participants |
| Sex: Female, Male Male | 2088 Participants | 2107 Participants | 4195 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 4,016 | 0 / 4,018 |
| other Total, other adverse events | 324 / 4,016 | 279 / 4,018 |
| serious Total, serious adverse events | 262 / 4,016 | 222 / 4,018 |
Outcome results
Primary
Number of Participants With Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI) Hospitalization Through the Respiratory Syncytial Virus Season
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths per minute (/min); 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. RSV season was the period of increased RSV infection.
Time frame: From dosing/randomization (Day 1) up to approximately 7 months
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI) Hospitalization Through the Respiratory Syncytial Virus Season | 11 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI) Hospitalization Through the Respiratory Syncytial Virus Season | 64 Participants |
Comparison: The 2-sided 95% confidence interval (CI) for the efficacy was calculated by an exact method assuming a binomial distribution of the number of RSV LRTI hospitalizations in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: <0.000195% CI: [69.493, 92.411]Exact method using binomial distribution
Secondary
Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection From Days 181 to 366 Post-dosing/Randomization
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with hospitalization for all-cause LRTI from Days 181 to 366 post-dosing/randomization (with no hospitalizations for all-cause LRTI before Day 181) is presented.
Time frame: From Day 181 to Day 366
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group. Only participants with data collected are reported.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection From Days 181 to 366 Post-dosing/Randomization | 68 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection From Days 181 to 366 Post-dosing/Randomization | 55 Participants |
Secondary
Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection From Days 366 to 731 Post-dosing/Randomization (for United Kingdom Reconsented Participants)
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with hospitalization for all-cause LRTI from Days 366 to 731 post-dosing/randomization (with no hospitalizations for all-cause LRTI before Day 366) in UK reconsented participants is presented.
Time frame: From Day 366 to Day 731
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group. Only participants with data collected are reported.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection From Days 366 to 731 Post-dosing/Randomization (for United Kingdom Reconsented Participants) | 18 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection From Days 366 to 731 Post-dosing/Randomization (for United Kingdom Reconsented Participants) | 10 Participants |
Secondary
Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with hospitalization for all-cause LRTI through 151 days post-dosing/randomization in France, UK, Germany, and overall is presented.
Time frame: From dosing/randomization (Day 1) to Day 151
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group. 'Number Analyzed' indicates the number of participants with data collected for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | Overall | 76 Participants |
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | France | 32 Participants |
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | United Kingdom | 35 Participants |
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | Germany | 9 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | Germany | 26 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | Overall | 132 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | United Kingdom | 58 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | France | 48 Participants |
Comparison: Statistical analysis for Overall:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of hospitalizations for all-cause LRTI through Day 151 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: <0.000195% CI: [24.677, 58.057]Exact method using binomial distribution
Comparison: Statistical analysis for France:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of hospitalizations for all-cause LRTI through Day 151 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.075495% CI: [-4.148, 59.648]Exact method using binomial distribution
Comparison: Statistical analysis for UK:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of hospitalizations for all-cause LRTI through Day 151 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.017795% CI: [8.211, 62.156]Exact method using binomial distribution
Comparison: Statistical analysis for Germany:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of hospitalizations for all-cause LRTI through Day 151 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.004695% CI: [25.952, 86.137]Exact method using binomial distribution
Secondary
Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 181 Days Post-dosing/Randomization
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with hospitalization for all-cause LRTI through 181 days post-dosing/randomization in France, UK, Germany, and overall is presented.
Time frame: From dosing/randomization (Day 1) to Day 181
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group. 'Number Analyzed' indicates the number of participants with data collected for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 181 Days Post-dosing/Randomization | Overall | 82 Participants |
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 181 Days Post-dosing/Randomization | United Kingdom | 38 Participants |
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 181 Days Post-dosing/Randomization | France | 34 Participants |
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 181 Days Post-dosing/Randomization | Germany | 10 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 181 Days Post-dosing/Randomization | Germany | 27 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 181 Days Post-dosing/Randomization | Overall | 138 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 181 Days Post-dosing/Randomization | France | 49 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through 181 Days Post-dosing/Randomization | United Kingdom | 62 Participants |
Comparison: Statistical analysis for Overall:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of hospitalizations for all-cause LRTI through day 181 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: <0.000195% CI: [23.073, 56.333]Exact method using binomial distribution
Comparison: Statistical analysis for France:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of hospitalizations for all-cause LRTI through day 181 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.100395% CI: [-7.188, 57.545]Exact method using binomial distribution
Comparison: Statistical analysis for UK:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of hospitalizations for all-cause LRTI through day 181 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.016495% CI: [8.449, 60.911]Exact method using binomial distribution
Comparison: Statistical analysis for Germany:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of hospitalizations for all-cause LRTI through day 181 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.005895% CI: [23.386, 84.478]Exact method using binomial distribution
Secondary
Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. RSV season was the period of increased RSV infection. Number of participants with hospitalization for all-cause LRTI through the RSV season in France, UK, Germany, and overall is presented.
Time frame: From dosing/randomization (Day 1) up to approximately 7 months
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group. 'Number Analyzed' indicates the number of participants with data collected for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season | Overall | 48 Participants |
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season | France | 24 Participants |
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season | United Kingdom | 17 Participants |
| Nirsevimab | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season | Germany | 7 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season | Germany | 23 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season | Overall | 106 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season | United Kingdom | 39 Participants |
| No Intervention | Number of Participants With Hospitalization for All-Cause Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season | France | 44 Participants |
Comparison: Statistical analysis for Overall:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of all-cause LRTI hospitalizations in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: <0.000195% CI: [40.36, 70.76]Exact method using binomial distribution
Comparison: Statistical analysis for France:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of all-cause LRTI hospitalizations in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.003995% CI: [20.121, 72.36]Exact method using binomial distribution
Comparison: Statistical analysis for UK:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of all-cause LRTI hospitalizations in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.002495% CI: [25.115, 78.049]Exact method using binomial distribution
Comparison: Statistical analysis for Germany:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of all-cause LRTI hospitalizations in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.003795% CI: [29.567, 89.396]Exact method using binomial distribution
Secondary
Number of Participants With Immediate Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were either events with the start date and time posterior to the start of the treatment period and up to the end of the treatment period or events with the start date and time prior to the start of the treatment period, whose severity was greater than 1 or missing and stop date is missing or not before the treatment period. Immediate events were recorded to capture medically relevant AEs which occurred within the first 30 minutes after immunization.
Time frame: Up to 30 minutes post-dosing/randomization on Day 1
Population: The Safety Analysis Set (SafAS) consisted of all participants who received nirsevimab in the study and all randomized participants who were randomized to the no intervention group and did not receive nirsevimab inadvertently. As pre-specified in the protocol and SAP, results are presented by treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirsevimab | Number of Participants With Immediate Treatment-Emergent Adverse Events (TEAEs) | 27 Participants |
| No Intervention | Number of Participants With Immediate Treatment-Emergent Adverse Events (TEAEs) | 0 Participants |
Secondary
Number of Participants With Non-Serious Treatment-Emergent Adverse Events
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were either events with the start date and time posterior to the start of the treatment period and up to the end of the treatment period or events with the start date and time prior to the start of the treatment period, whose severity was greater than 1 or missing and stop date was missing or not before the treatment period.
Time frame: From dosing/randomization (Day 1) to Day 31
Population: The SafAS consisted of all participants who received nirsevimab in the study and all randomized participants who were randomized to the no intervention group and did not receive nirsevimab inadvertently. As pre-specified in the protocol and SAP, results are presented by treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirsevimab | Number of Participants With Non-Serious Treatment-Emergent Adverse Events | 1316 Participants |
| No Intervention | Number of Participants With Non-Serious Treatment-Emergent Adverse Events | 1265 Participants |
Secondary
Number of Participants With Recurrent Wheeze (for United Kingdom Reconsented Participants)
Wheeze was defined as a physician-diagnosed wheeze or asthma or related ear, nose and throat (ENT)/respiratory symptoms at an office visit or an illness for which the child was prescribed medication to treat an ENT/respiratory condition. Recurrent wheeze event was defined as 2 or more protocol-defined wheeze episodes throughout follow-up period.
Time frame: From dosing/randomization (Day 1) to Day 731
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group. Only participants with data collected are reported.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirsevimab | Number of Participants With Recurrent Wheeze (for United Kingdom Reconsented Participants) | 101 Participants |
| No Intervention | Number of Participants With Recurrent Wheeze (for United Kingdom Reconsented Participants) | 96 Participants |
Secondary
Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 181 to 366 Post-dosing/Randomization
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with RSV LRTI hospitalization from Days 181 to 366 post-dosing/randomization (with no RSV LRTI hospitalizations before Day 181) in France, UK, Germany, and overall is presented.
Time frame: From Day 181 to Day 366
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group. Only participants with data collected are reported. 'Number Analyzed' indicates the number of participants with data collected for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 181 to 366 Post-dosing/Randomization | Overall | 31 Participants |
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 181 to 366 Post-dosing/Randomization | France | 6 Participants |
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 181 to 366 Post-dosing/Randomization | United Kingdom | 20 Participants |
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 181 to 366 Post-dosing/Randomization | Germany | 5 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 181 to 366 Post-dosing/Randomization | Germany | 4 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 181 to 366 Post-dosing/Randomization | Overall | 28 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 181 to 366 Post-dosing/Randomization | United Kingdom | 19 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 181 to 366 Post-dosing/Randomization | France | 5 Participants |
Secondary
Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 366 to 731 Post-dosing/Randomization (for United Kingdom Reconsented Participants)
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with RSV LRTI hospitalization from Days 366 to 731 post-dosing/randomization (with no RSV LRTI hospitalizations before Day 366) in UK reconsented participants is presented.
Time frame: From Day 366 to Day 731
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group. Only participants with data collected are reported.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 366 to 731 Post-dosing/Randomization (for United Kingdom Reconsented Participants) | 7 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization From Days 366 to 731 Post-dosing/Randomization (for United Kingdom Reconsented Participants) | 2 Participants |
Secondary
Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 151 Days Post-dosing/Randomization
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with RSV LRTI hospitalization through 151 days post-dosing/randomization in France, UK, Germany, and overall is presented.
Time frame: From dosing/randomization (Day 1) to Day 151
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group. 'Number Analyzed' indicates the number of participants with data collected for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 151 Days Post-dosing/Randomization | Overall | 12 Participants |
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 151 Days Post-dosing/Randomization | France | 4 Participants |
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 151 Days Post-dosing/Randomization | United Kingdom | 3 Participants |
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 151 Days Post-dosing/Randomization | Germany | 5 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 151 Days Post-dosing/Randomization | Germany | 19 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 151 Days Post-dosing/Randomization | Overall | 67 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 151 Days Post-dosing/Randomization | United Kingdom | 20 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 151 Days Post-dosing/Randomization | France | 28 Participants |
Comparison: Statistical analysis for Overall:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of RSV LRTI hospitalizations in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: <0.000195% CI: [67.271, 91.357]Exact method using binomial distribution
Comparison: Statistical analysis for France:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of RSV LRTI hospitalizations in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: <0.000195% CI: [60.283, 96.459]Exact method using binomial distribution
Comparison: Statistical analysis for UK:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of RSV LRTI hospitalizations in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.000495% CI: [50.084, 97.183]Exact method using binomial distribution
Comparison: Statistical analysis for Germany:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of RSV LRTI hospitalizations in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.005595% CI: [29.006, 92.518]Exact method using binomial distribution
Secondary
Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 181 Days Post-dosing/Randomization
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with RSV LRTI hospitalization through 181 days post-dosing/randomization in France, UK, Germany, and overall is presented.
Time frame: From dosing/randomization (Day 1) to Day 181
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group. 'Number Analyzed' indicates the number of participants with data collected for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 181 Days Post-dosing/Randomization | Overall | 12 Participants |
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 181 Days Post-dosing/Randomization | France | 4 Participants |
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 181 Days Post-dosing/Randomization | United Kingdom | 3 Participants |
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 181 Days Post-dosing/Randomization | Germany | 5 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 181 Days Post-dosing/Randomization | Germany | 19 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 181 Days Post-dosing/Randomization | Overall | 68 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 181 Days Post-dosing/Randomization | United Kingdom | 21 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through 181 Days Post-dosing/Randomization | France | 28 Participants |
Comparison: Statistical analysis for Overall:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of RSV LRTI hospitalizations through Day 181 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: <0.000195% CI: [67.826, 91.49]Exact method using binomial distribution
Comparison: Statistical analysis for France:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of RSV LRTI hospitalizations through Day 181 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: <0.000195% CI: [60.34, 96.464]Exact method using binomial distribution
Comparison: Statistical analysis for UK:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of RSV LRTI hospitalizations through Day 181 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.000295% CI: [52.85, 97.311]Exact method using binomial distribution
Comparison: Statistical analysis for Germany:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of RSV LRTI hospitalizations through Day 181 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.005495% CI: [29.077, 92.525]Exact method using binomial distribution
Secondary
Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through the Respiratory Syncytial Virus Season in Each Country
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Hospitalization was defined as the decision to admit to in-patient care by the treating physician. RSV season was the period of increased RSV infection. Number of participants with RSV LRTI hospitalization through the RSV season in France, UK, and Germany is presented.
Time frame: From dosing/randomization (Day 1) up to approximately 7 months
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group. 'Number Analyzed' indicates the number of participants with data collected for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through the Respiratory Syncytial Virus Season in Each Country | France | 3 Participants |
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through the Respiratory Syncytial Virus Season in Each Country | United Kingdom | 3 Participants |
| Nirsevimab | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through the Respiratory Syncytial Virus Season in Each Country | Germany | 5 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through the Respiratory Syncytial Virus Season in Each Country | France | 28 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through the Respiratory Syncytial Virus Season in Each Country | United Kingdom | 17 Participants |
| No Intervention | Number of Participants With Respiratory Syncytial Virus Lower Respiratory Tract Infection Hospitalization Through the Respiratory Syncytial Virus Season in Each Country | Germany | 19 Participants |
Comparison: Statistical analysis for France: The adjusted 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of RSV LRTI hospitalizations in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization. Adjustment based on Bonferroni-Holm procedure.p-value: <0.000195% CI: [63.676, 98.813]Exact method using binomial distribution
Comparison: Statistical analysis for UK: The adjusted 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of RSV LRTI hospitalizations in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization. Adjustment based on Bonferroni-Holm procedure.p-value: 0.003695% CI: [33.589, 97.593]Exact method using binomial distribution
Comparison: Statistical analysis for Germany: The adjusted 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of RSV LRTI hospitalizations in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization. Adjustment based on Bonferroni-Holm procedure.p-value: 0.005195% CI: [29.74, 92.595]Exact method using binomial distribution
Secondary
Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events of Special Interest (AESIs) and Treatment-Emergent Medically Attended Adverse Events (MAAEs)
AE: untoward medical occurrence in clinical study participant, temporally associated with use of study intervention, whether or not related to it. TEAEs: events with start date/time posterior to start of treatment period(TP) and up to end of TP, or events with start date/time prior to start of TP, whose severity was\>1/missing; stop date was missing/not before TP. SAE: AE at any dose resulting in death, persistent or significant disability/incapacity, required inpatient hospitalization/prolongation of existing hospitalization, was life-threatening or congenital anomaly/birth defect or medically important event. MAAE: new onset/worsening of condition that prompted participant or participant's parent/legally acceptable representative to seek unplanned medical advice at physician's office/Emergency Department. AESI: scientific, medical concern specific to Sponsor's study intervention/program for which ongoing monitoring and rapid communication by investigator to Sponsor was appropriate.
Time frame: From dosing/randomization (Day 1) to Day 366
Population: The SafAS consisted of all participants who received nirsevimab in the study and all randomized participants who were randomized to the no intervention group and did not receive nirsevimab inadvertently. As pre-specified in the protocol and SAP, results are presented by treatment group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirsevimab | Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events of Special Interest (AESIs) and Treatment-Emergent Medically Attended Adverse Events (MAAEs) | Treatment-emergent SAEs | 262 Participants |
| Nirsevimab | Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events of Special Interest (AESIs) and Treatment-Emergent Medically Attended Adverse Events (MAAEs) | Treatment-emergent AESIs | 11 Participants |
| Nirsevimab | Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events of Special Interest (AESIs) and Treatment-Emergent Medically Attended Adverse Events (MAAEs) | Treatment-emergent MAAEs | 3106 Participants |
| No Intervention | Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events of Special Interest (AESIs) and Treatment-Emergent Medically Attended Adverse Events (MAAEs) | Treatment-emergent SAEs | 222 Participants |
| No Intervention | Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events of Special Interest (AESIs) and Treatment-Emergent Medically Attended Adverse Events (MAAEs) | Treatment-emergent AESIs | 3 Participants |
| No Intervention | Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events of Special Interest (AESIs) and Treatment-Emergent Medically Attended Adverse Events (MAAEs) | Treatment-emergent MAAEs | 3100 Participants |
Secondary
Number of Participants With Treatment-Related Serious Adverse Event (for United Kingdom Reconsented Participants)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were either events with the start date and time posterior to the start of the treatment period and up to the end of the treatment period or events with the start date and time prior to the start of the treatment period, whose severity was greater than 1 or missing and stop date is missing or not before the treatment period. SAE: AE at any dose resulting in death, persistent or significant disability/incapacity, required inpatient hospitalization/prolongation of existing hospitalization, was life-threatening or congenital anomaly/birth defect or medically important event. A treatment-related TEAE was a TEAE considered by the investigator as related or with unknown/missing relationship to treatment for participants who received nirsevimab on Day 1.
Time frame: From Day 366 to Day 731
Population: The SafAS consisted of all participants who received nirsevimab in the study and all randomized participants who were randomized to the no intervention group and did not receive nirsevimab inadvertently. As pre-specified in the protocol and SAP, results are presented by treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirsevimab | Number of Participants With Treatment-Related Serious Adverse Event (for United Kingdom Reconsented Participants) | 0 Participants |
| No Intervention | Number of Participants With Treatment-Related Serious Adverse Event (for United Kingdom Reconsented Participants) | 0 Participants |
Secondary
Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Very severe RSV LRTI was defined as RSV LRTI hospitalization with oxygen saturation \<90% (at any time during hospitalization) and oxygen supplementation. Hospitalization was defined as the decision to admit to in-patient care by the treating physician. Number of participants with very severe RSV LRTI through 151 days post-dosing/randomization in France, UK, Germany, and overall is presented.
Time frame: From dosing/randomization (Day 1) to Day 151
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group. 'Number Analyzed' indicates the number of participants with data collected for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirsevimab | Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | Overall | 6 Participants |
| Nirsevimab | Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | France | 2 Participants |
| Nirsevimab | Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | United Kingdom | 1 Participants |
| Nirsevimab | Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | Germany | 3 Participants |
| No Intervention | Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | Germany | 4 Participants |
| No Intervention | Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | Overall | 24 Participants |
| No Intervention | Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | United Kingdom | 11 Participants |
| No Intervention | Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through 151 Days Post-dosing/Randomization | France | 9 Participants |
Comparison: Statistical analysis for Overall:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of very severe RSV LRTI through Day 151 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.001395% CI: [38.012, 91.747]Exact method using binomial distribution
Comparison: Statistical analysis for Germany:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of very severe RSV LRTI through Day 151 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.985195% CI: [-337.329, 89.162]Exact method using binomial distribution
Comparison: Statistical analysis for France:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of very severe RSV LRTI through Day 151 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.06295% CI: [-5.823, 97.697]Exact method using binomial distribution
Comparison: Statistical analysis for UK:~The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of very severe RSV LRTI through Day 151 post-dosing/randomization in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.00695% CI: [38.156, 99.791]Exact method using binomial distribution
Secondary
Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season
LRTI included the following common symptoms: clinical finding of rhonchi, rales, crackles, or wheeze; increased respiratory rate at rest (age: \<2 months, ≥60 breaths/min; 2 to 6 months, ≥50 breaths/min; \>6 months, ≥40 breaths/min), and hypoxemia (in room air: oxygen saturation \<95%). Very severe RSV LRTI was defined as RSV LRTI hospitalization with oxygen saturation \<90% (at any time during hospitalization) and oxygen supplementation. Hospitalization was defined as the decision to admit to in-patient care by the treating physician. RSV season was the period of increased RSV infection.
Time frame: From dosing/randomization (Day 1) up to approximately 7 months
Population: The All Randomized Set consisted of all participants randomly assigned to either the nirsevimab group or the no intervention group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirsevimab | Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season | 5 Participants |
| No Intervention | Number of Participants With Very Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection Through the Respiratory Syncytial Virus Season | 21 Participants |
Comparison: The 2-sided 95% CI for the efficacy was calculated by an exact method assuming a binomial distribution of the number of very severe RSV LRTI in the nirsevimab group conditional on the total number in both groups accounting for the follow-up time post-dosing/randomization.p-value: 0.001495% CI: [39.249, 93.432]Exact method using binomial distribution