Safety and Immunogenicity of Fluzone® Quadrivalent Vaccine Administered to Healthy Children

Safety and Immunogenicity of Fluzone® Quadrivalent Vaccine Administered to Healthy Children 6 to < 36 Months of Age

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Fluzone Quadrivalent vaccine, No Preservative; Biological: Fluzone Quadrivalent vaccine, No Preservative

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.

• Study Type: Interventional
• Enrollment (Actual): 1950
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • California
    • Anaheim, California, United Kingdom, 92804
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
  • Arkansas
    • Harrisburg, Arkansas, United States, 72432
  • California
    • Downey, California, United States, 90241
    • Paramount, California, United States, 90723
    • Sacramento, California, United States, 95815
    • San Diego, California, United States, 92111
  • Colorado
    • Thornton, Colorado, United States, 80233
  • Florida
    • Miami, Florida, United States, 33142
    • Miami Beach, Florida, United States, 33140
  • Idaho
    • Meridian, Idaho, United States, 83642
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
  • Louisiana
    • Metairie, Louisiana, United States, 70006
  • Nebraska
    • Lincoln, Nebraska, United States, 68504
    • Lincoln, Nebraska, United States, 68505
    • Lincoln, Nebraska, United States, 68516
    • Norfolk, Nebraska, United States, 68701
    • Omaha, Nebraska, United States, 68134
    • Omaha, Nebraska, United States, 68131
  • New York
    • Syracuse, New York, United States, 13057
  • Ohio
    • Dayton, Ohio, United States, 45414
    • Grove City, Ohio, United States, 43123
  • Oregon
    • Gresham, Oregon, United States, 97030
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16505
  • South Carolina
    • Charleston, South Carolina, United States, 29407
    • Charleston, South Carolina, United States, 29414
  • Tennessee
    • Tullahoma, Tennessee, United States, 37388
  • Texas
    • Fort Worth, Texas, United States, 76107
    • Houston, Texas, United States, 77055
  • Utah
    • Layton, Utah, United States, 84041
    • Orem, Utah, United States, 84057
    • Provo, Utah, United States, 84604
    • Roy, Utah, United States, 84067
    • South Jordan, Utah, United States, 84095
    • West Jordan, Utah, United States, 84088
  • Virginia
    • Burke, Virginia, United States, 22015

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 2 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fluzone Quadrivalent Vaccine, 0.25-mL; Participants received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.25-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.	Biological: Fluzone Quadrivalent vaccine, No Preservative; 0.25-mL (Pediatric Dose), Intramuscular (2016-2017 formulation); Other Names: Fluzone® Quadrivalent Influenza Vaccine; Biological: Fluzone Quadrivalent vaccine, No Preservative; 0.5-mL, Intramuscular (2016-2017 formulation); Other Names: Fluzone® Quadrivalent Influenza Vaccine
Experimental: Fluzone Quadrivalent Vaccine, 0.5-mL; Participants received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.5-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28.	Biological: Fluzone Quadrivalent vaccine, No Preservative; 0.25-mL (Pediatric Dose), Intramuscular (2016-2017 formulation); Other Names: Fluzone® Quadrivalent Influenza Vaccine; Biological: Fluzone Quadrivalent vaccine, No Preservative; 0.5-mL, Intramuscular (2016-2017 formulation); Other Names: Fluzone® Quadrivalent Influenza Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Fever (Fever Rate) Following Vaccination With Fluzone Quadrivalent Vaccine	Fever rate was defined as percentage of participants with fever (temperature >=100.4 degrees Fahrenheit [38.0 degrees Celsius]) following vaccination with Fluzone Quadrivalent vaccine.	Within 7 days after any vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies	Anti-influenza antibodies were measured using a hemagglutination inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage.	28 days post-final vaccination
Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens	Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. SCR was defined as percentage of participants with either a pre-vaccination titer <10 (1/dil) and a post-final vaccination titer >=40 (1/dil), or a pre-vaccination titer >=10 (1/dil) and at least a four-fold increase in post-final vaccination titer.	28 days post-final vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 23, 2016
• Primary Completion (Actual): March 6, 2017
• Study Completion (Actual): March 6, 2017

Study Registration Dates

• First Submitted: September 23, 2016
• First Submitted That Met QC Criteria: September 23, 2016
• First Posted (Estimate): September 27, 2016

Study Record Updates

• Last Update Posted (Actual): March 29, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Influenza; Influenza virus vaccine; Fluzone® Quadrivalent Influenza Vaccine (No Preservative)
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: GRC88; U1111-1143-9273 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org