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

• ClinicalTrials.gov Identifier: NCT02915302
• Recruitment Status: Completed
• First Posted: September 27, 2016
• Results First Posted: April 3, 2018
• Last Update Posted: March 29, 2022
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: Fluzone Quadrivalent vaccine, No Preservative	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1950 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity of Fluzone® Quadrivalent Vaccine Administered to Healthy Children 6 to < 36 Months of Age
• Study Start Date: September 23, 2016
• Actual Primary Completion Date: March 6, 2017
• Actual Study Completion Date: March 6, 2017

Arms and Interventions

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 Name: 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; 0.5-mL, Intramuscular (2016-2017 formulation); Other Name: Fluzone® Quadrivalent Influenza Vaccine

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Fever (Fever Rate) Following Vaccination With Fluzone Quadrivalent Vaccine [ Time Frame: Within 7 days after any vaccination ]
   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.

Secondary Outcome Measures :

1. Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies [ Time Frame: 28 days post-final vaccination ]
   Anti-influenza antibodies were measured using a hemagglutination inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage.
2. Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens [ Time Frame: 28 days post-final vaccination ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 35 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, Alabama

Birmingham, Alabama, United States, 35205

United States, Arkansas

Harrisburg, Arkansas, United States, 72432

United States, California

Downey, California, United States, 90241

Paramount, California, United States, 90723

Sacramento, California, United States, 95815

San Diego, California, United States, 92111

United States, Colorado

Thornton, Colorado, United States, 80233

United States, Florida

Miami Beach, Florida, United States, 33140

Miami, Florida, United States, 33142

United States, Idaho

Meridian, Idaho, United States, 83642

United States, Kentucky

Bardstown, Kentucky, United States, 40004

United States, Louisiana

Metairie, Louisiana, United States, 70006

United States, 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, 68131

Omaha, Nebraska, United States, 68134

United States, New York

Syracuse, New York, United States, 13057

United States, Ohio

Dayton, Ohio, United States, 45414

Grove City, Ohio, United States, 43123

United States, Oregon

Gresham, Oregon, United States, 97030

United States, Pennsylvania

Erie, Pennsylvania, United States, 16505

United States, South Carolina

Charleston, South Carolina, United States, 29407

Charleston, South Carolina, United States, 29414

United States, Tennessee

Tullahoma, Tennessee, United States, 37388

United States, Texas

Fort Worth, Texas, United States, 76107

Houston, Texas, United States, 77055

United States, 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

United States, Virginia

Burke, Virginia, United States, 22015

United Kingdom

Anaheim, California, United Kingdom, 92804

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director; Sanofi Pasteur Inc.

  Study Documents (Full-Text)

Documents provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Study Protocol  [PDF] June 13, 2016

Statistical Analysis Plan  [PDF] July 20, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02915302
• Other Study ID Numbers: GRC88; U1111-1143-9273 ( Other Identifier: WHO )
• First Posted: September 27, 2016
• Results First Posted: April 3, 2018
• Last Update Posted: March 29, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Influenza; Influenza virus vaccine; Fluzone® Quadrivalent Influenza Vaccine (No Preservative)

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs