Study on a High-Dose Quadrivalent Influenza Vaccine Compared With Standard-Dose Quadrivalent Influenza Vaccine in Children 6 Months Through 35 Months of Age

Efficacy, Immunogenicity, and Safety of High-Dose Quadrivalent Influenza Vaccine Compared With Standard-Dose Quadrivalent Influenza Vaccine in Children 6 Months Through 35 Months of Age

The primary objective of the study was to compare the clinical efficacy of high-dose quadrivalent influenza vaccine (QIV-HD) to standard-dose quadrivalent influenza vaccine (QIV-SD) in participants 6 months through 35 months of age for the prevention of laboratory-confirmed influenza illness caused by any influenza A or B type.

The secondary objectives of the study were:

• To compare QIV-HD to QIV-SD:
• in participants 6 months through 35 months of age for the prevention of laboratory-confirmed influenza illness caused by any influenza A or B type using a more stringent threshold
• in participants 6 months through 35 months of age for the prevention of laboratory-confirmed protocol-defined influenza-like illness caused by viral strains similar to those contained in the vaccine.
• in participants 6 months through 23 months of age for the prevention of laboratory-confirmed influenza illness caused by any influenza A or B types.
• To compare hemagglutination inhibition (HAI) immune response of QIV-HD to QIV-SD in participants 6 months through 35 months of age
• To describe the HAI, seroneutralization (SN), and anti-neuraminidase (NA) immune response
• To describe the immune response to revaccination in Season 3 (Northern Hemisphere)
• To describe the safety profile of each vaccine

The study was planned to start in the second half of 2020 with the Sentinel Safety Cohort. Following the Sentinel Safety Cohort, the main efficacy cohort was to be conducted during the 2021-2022 Northern Hemisphere influenza season (Season 1), the 2021-2022 Southern Hemisphere influenza season (Season 2), and the 2021-2022-2023 Northern Hemisphere influenza season (Season 3).

Participants received either 1 or 2 doses of the study vaccine depending on whether they were previously influenza vaccinated or previously influenza unvaccinated, respectively.

Study duration per participant was approximately 6 to 7 months.

Inclusion criteria :

• Aged 6 to 35 months on the day of the first study visit
• Informed consent form was signed and dated by the parent(s) or guardian(s) and by an independent witness, if required by local regulations.
• Participant and parent / guardian who were able to attend all scheduled visits and to comply with all study procedures.
• Covered by health insurance if required by local regulations
• For Season 3 Re-vaccination Cohort: eligible participants must have been enrolled in the Season 1 (2021-2022 Northern Hemisphere season) immunogenicity subset and must have completed all study procedures (ie, blood draws and vaccinations) in Season 1.

Exclusion criteria:

• Participation at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.
• For all participants: Receipt of any vaccine in the 30 days preceding the first study vaccination. For participants in immunogenicity subset: Planned receipt of any vaccine before Visit 2 for participants receiving 1 dose of influenza vaccine or Visit 3 for participants receiving 2 doses of influenza vaccine.
• Previous vaccination against influenza in the preceding 6 months with either the study vaccine or another influenza vaccine
• Receipt of immune globulins, blood or blood-derived products in the past 3 months.
• Known or suspected congenital or acquired immunodeficiency (eg, HIV); 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).
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances. Exception: participants with an egg allergy are allowed to enroll in the study.
• Thrombocytopenia, bleeding disorder, or receipt of anticoagulants that based on Investigator's judgment contraindicate intramuscular vaccination
• Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with study conduct or completion.
• Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0 C [≥ 100.4 F]). A prospective participant would not be included in the study until the condition was resolved or the febrile event was subsided.
• Identified as natural or adopted child of the Investigator or employee with direct involvement in the proposed study.
• Personal or family history of Guillain-Barre Syndrome.
• Any condition that in the opinion of the Investigator would pose a health risk to the participant if enrolled or could interfere with the evaluation of the vaccine.
• Personal history of clinically significant development delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder.
• For Season 3 (2022-2023 Northern Hemisphere) main cohort: participants who were enrolled in a previous study season are excluded from Season 3, with the exception of the Re-vaccination Cohort.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.