Clinical trial NCT02915302: Safety and Immunogenicity of Fluzone® Quadrivalent Vaccine Administered to Healthy Children
Official title: Safety and Immunogenicity of Fluzone® Quadrivalent Vaccine Administered to Healthy Children 6 to < 36 Months of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Influenza
Keywords: Influenza
Influenza virus vaccine
Fluzone® Quadrivalent Influenza Vaccine (No Preservative)
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-09-27
Enrollment: 1950
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of the study was to describe the safety and immunogenicity of a 0.5-mL dose (15 μg hemagglutinin \[HA\] per strain) of Fluzone Quadrivalent vaccine in children 6 to \<36 months of age.

Primary objective:

* To compare the rate of any fever (temperature ≥100.4 degrees Fahrenheit \[38.0 degrees Celsius) following a 0.5-mL dose of Fluzone Quadrivalent vaccine to that following a 0.25-mL dose of Fluzone Quadrivalent vaccine during the 7 days after either vaccination (Dose 1 and Dose 2 combined) in participants 6 to \< 36 months of age.

Secondary objective:

* To compare antibody responses induced by a 0.5-mL dose of Fluzone Quadrivalent vaccine to those induced by a 0.25-mL dose of Fluzone Quadrivalent vaccine as assessed by geometric mean titer (GMT) ratios and seroconversion rate differences after the final vaccination in participants 6 to \< 36 months of age.

Other objectives:

* To describe the safety of 2 different dose levels of the 2016-2017 formulation of Fluzone Quadrivalent vaccine in participants 6 to \< 36 months of age.
* To describe the immunogenicity of 2 different dose levels of the 2016-2017 formulation of Fluzone Quadrivalent vaccine in participants 6 months to \< 36 months of age.
* To submit available sera from approximately 30 participants to the Center for Biologics Evaluation and Research for further analysis by the World Health Organization, the Centers for Disease Control and Prevention, and the FDA to support formulation recommendations for subsequent influenza vaccines.

Detailed description: All participants received 1 intramuscular dose of Fluzone Quadrivalent vaccine during Visit 1. For participants, for whom 2 doses of influenza vaccine were recommended per Advisory Committee on Immunization Practices (ACIP) guidance, a second dose of Fluzone Quadrivalent vaccine (of the same volume as the first dose) was administered during Visit 2 (28 days after Visit 1).

Solicited adverse event (AE) information was collected for 7 days after each vaccination, unsolicited AE information was collected from Visit 1 to Visit 2 or to Visit 3 for participants receiving 2 doses of study vaccine. Serious adverse event (SAE) information was collected for 28 days after each vaccination.

Immunogenicity was evaluated in a planned subset of 1600 randomly selected participants prior to vaccination on Day 0 (Visit 1) and at Day 28 after the final vaccination.

Eligibility criteria: Inclusion Criteria:

* Aged 6 to \< 36 months of age on the day of first study vaccination (study product administration).
* Born at full term of pregnancy (≥37 weeks) and/or with a birth weight ≥2.5 kg. Note: This inclusion criterion only applies to participants 6 to \<12 months of age on the day of the first study visit.
* Informed consent form has been signed and dated by the parent(s) or guardian(s).
* Participant and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

* Participation at the time of study enrollment (or in the 30 days preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
* Receipt of any vaccine in the 30 days preceding the first trial vaccination, or 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 2016-2017 season) with either the trial vaccine or another vaccine.
* Receipt of immune globulins, blood, or blood-derived products in the past 3 months.
* 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).
* Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances.
* Thrombocytopenia, which may be a contraindication for intramuscular vaccination, at the discretion of the Investigator.
* Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination.
* Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
* Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion.
* Moderate or severe acute illness/infection (according to Investigator judgment) on the day of planned vaccination or febrile illness (temperature ≥100.4 degrees Fahrenheit \[38.0 degrees Celsius\]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
* Identified as a natural or adopted child of either the Investigator or an employee with direct involvement in the proposed study.
* History of serious adverse reactions to any influenza vaccine.
* Personal history of Guillain-Barré 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 developmental delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder.
* Known seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C.

Primary outcomes:
measure: Percentage of Participants With Fever (Fever Rate) Following Vaccination With Fluzone Quadrivalent Vaccine
timeFrame: Within 7 days after any vaccination
Secondary outcomes:
measure: Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies
timeFrame: 28 days post-final vaccination
measure: Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens
timeFrame: 28 days post-final vaccination
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Harrisburg
country: United States
state: Arkansas
city: Downey
country: United States
state: California
city: Paramount
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Thornton
country: United States
state: Colorado
city: Miami Beach
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Meridian
country: United States
state: Idaho
city: Bardstown
country: United States
state: Kentucky
city: Metairie
country: United States
state: Louisiana
city: Lincoln
country: United States
state: Nebraska
city: Lincoln
country: United States
state: Nebraska
city: Lincoln
country: United States
state: Nebraska
city: Norfolk
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Syracuse
country: United States
state: New York
city: Dayton
country: United States
state: Ohio
city: Grove City
country: United States
state: Ohio
city: Gresham
country: United States
state: Oregon
city: Erie
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Charleston
country: United States
state: South Carolina
city: Tullahoma
country: United States
state: Tennessee
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Layton
country: United States
state: Utah
city: Orem
country: United States
state: Utah
city: Provo
country: United States
state: Utah
city: Roy
country: United States
state: Utah
city: South Jordan
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Burke
country: United States
state: Virginia
city: Anaheim
country: United Kingdom
state: California
Study officials:
affiliation: Sanofi Pasteur Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Robertson CA, Mercer M, Selmani A, Klein NP, Jeanfreau R, Greenberg DP. Safety and Immunogenicity of a Full-dose, Split-virion, Inactivated, Quadrivalent Influenza Vaccine in Healthy Children 6-35 Months of Age: A Randomized Controlled Clinical Trial. Pediatr Infect Dis J. 2019 Mar;38(3):323-328. doi: 10.1097/INF.0000000000002227.