Clinical trial NCT04544267: Study on a High-Dose Quadrivalent Influenza Vaccine Compared With Standard-Dose Quadrivalent Influenza Vaccine in Children 6 Months Through 35 Months of Age
Official title: 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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE3
Conditions: Influenza
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-09-10
Enrollment: 13320
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A sentinel safety cohort is selected for collection safety events where QIV-HD will be administered open-label in 100 participants. These subjects will not provide blood samples and will not be followed for influenza-like illness (ILI) surveillance.

A re-vaccination cohort will be composed of a subset of approximately 120 participants from Season 1 (2021-2022 Northern Hemisphere) will be re-enrolled and re-randomized in Season 3.The re-vaccination cohort will be included re-randomized to receive either QIV-HD or QIV-SD, will provide blood samples in Season 1 and Season 3, and will not be followed for ILI surveillance during their participation in Season 3.
Primary purpose: PREVENTION

Brief summary: The primary objective of the study is 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 are:

* 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

Detailed description: The study is planned to start in the second half of 2020 with the Sentinel Safety Cohort. Following the Sentinel Safety Cohort, the main efficacy cohort will 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 will receive 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 is approximately 6 to 7 months.

Eligibility criteria: Inclusion criteria :

* Aged 6 to 35 months on the day of the first study visit
* Informed consent form has been signed and dated by the parent(s) or guardian(s) and by an independent witness, if required by local regulations.
* Participant and parent / guardian are 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, is 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 should not be included in the study until the condition has resolved or the febrile event has 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.

Primary outcomes:
measure: Number of participants with laboratory-confirmed influenza illness caused by any influenza viral types/subtypes, in association with a protocol-defined influenza-like illness (ILI)
timeFrame: From 14 days after the first injection to 6 months after the last injection
Secondary outcomes:
measure: Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI laboratory-confirmed as positive in participants aged 6 through 23 months for any influenza A or B type
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI laboratory-confirmed as positive for any influenza A or B type, according to previous vaccination status
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine, according to previous vaccination status
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI laboratory-confirmed as positive for any influenza A or B type, and associated with acute otitis media (AOM)
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine, and associated with AOM
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI laboratory-confirmed as positive for any influenza A or B type, and associated with acute lower respiratory infection (ALRI)
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine, and associated with ALRI
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI PCR-confirmed as positive for viral strains similar to those contained in the vaccine
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI culture-confirmed as positive for viral strains similar to those contained in the vaccine
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI PCR-confirmed as positive for any influenza A or B types
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI culture-confirmed as positive for any influenza A or B types
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI laboratory-confirmed as positive for any influenza A or B types and associated with hospitalization
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine and associated with hospitalization
timeFrame: From 14 days to maximum 6 months after the last injection
measure: Geometric mean titer of influenza vaccine antibodies
timeFrame: Day 0 and 28 days after the last vaccination
measure: Number of participants with seroconversion or significant increase of titers
timeFrame: Day 0 and 28 days after the last vaccination
measure: Number of participants with influenza vaccine antibody titer ≥ 10 (1/dilution [dil])
timeFrame: Day 0 and 28 days after the last vaccination
measure: Influenza vaccine antibody titer ratio
timeFrame: Day 0 and 28 days after the last vaccination
measure: Participant with influenza vaccine antibody titer ≥ 40 (1/dil)
timeFrame: Day 0 and 28 days after the last vaccination
measure: Influenza SN antibody titer
timeFrame: Day 0 and 28 days after the last vaccination
measure: Influenza SN antibody titer ratio
timeFrame: 28 days after the last vaccination
measure: Number of participants with influenza SN antibody titer above predefined thresholds
timeFrame: 28 days after the last vaccination
measure: Fold-increase in influenza SN antibody titer
timeFrame: 28 days after the last vaccination
measure: Detectable influenza SN antibody titer
timeFrame: Day 0 and 28 days after the last vaccination
measure: Anti-NA antibody titer
timeFrame: Day 0 and 28 days after the last vaccination
measure: Anti-NA antibody titer ratio
timeFrame: 28 days after the last vaccination
measure: Number of participants with anti-NA antibody titer above predefined thresholds
timeFrame: 28 days after the last vaccination
measure: Fold-increase in anti-NA antibody titer
timeFrame: 28 days after the last vaccination
measure: Detectable anti-NA antibody titer
timeFrame: Day 0 and 28 days after the last vaccination
measure: Number of participants with immediate adverse events
timeFrame: Within 30 minutes after vaccination
measure: Number of participants with solicited injection site and systemic reactions
timeFrame: Within 7 days after vaccination
measure: Number of participants with unsolicited adverse events
timeFrame: Within 28 days after vaccination
measure: Number of participants with serious adverse events
timeFrame: From Day 0 to Day 180
measure: Number of participants with adverse events of special interest
timeFrame: From Day 0 to Day 180
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Investigational Site Number :8400008
state: California
city: Miami
country: United States
facility: Investigational Site Number :8400007
state: Florida
city: Atlanta
country: United States
facility: Investigational Site Number :8400001
state: Georgia
city: El Dorado
country: United States
facility: Investigational Site Number :8400032
state: Kansas
city: Bardstown
country: United States
facility: Investigational Site Number :8400005
state: Kentucky
city: Metairie
country: United States
facility: Investigational Site Number :8400009
state: Louisiana
city: Dayton
country: United States
facility: Investigational Site Number :8400027
state: Ohio
city: Barnwell
country: United States
facility: Investigational Site Number :8400033
state: South Carolina
city: Salt Lake City
country: United States
facility: Investigational Site Number :8400006
state: Utah
city: Salt Lake City
country: United States
facility: Investigational Site Number :8400045
state: Utah
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: