Safety and Immunogenicity of Fluzone® Quadrivalent, Flublok® Quadrivalent, and Fluzone® High-Dose, Influenza Vaccines, 2018-2019 Formulations (GRC90)

The primary objectives of this study were:

• To describe the immunogenicity of the 2018-2019 formulation of Fluzone® Quadrivalent vaccine in children 6 to less than (<) 36 months of age and 3 to <9 years of age, and in adults 18 to <65 years of age; the immunogenicity of the 2018-2019 formulation of Flublok® Quadrivalent vaccine in adults 18 to <65 years of age; and the immunogenicity of the 2018-2019 formulation of Fluzone High-Dose vaccine in adults greater than or equal to (>=) 65 years of age.
• To describe the safety of the 2018-2019 formulation of Fluzone Quadrivalent vaccine in children 6 to <36 months of age and 3 to <9 years of age, and in adults 18 to <65 years of age; the safety of the 2018-2019 formulation of Flublok Quadrivalent vaccine in adults 18 to <65 years of age; and the safety of the 2018-2019 formulation of Fluzone High-Dose vaccine in adults >=65 years of age.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Fluzone Quadrivalent vaccine, 2018-2019 formulation; Biological: Flublok Quadrivalent vaccine, 2018-2019 formulation; Biological: Fluzone High-Dose vaccine, 2018-2019 formulation

Detailed Description

Study duration per participant was approximately 21 days for adult participants or 28 days for child participants who received one dose of vaccine, and 56 days for participants who received two doses of vaccine.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Investigational Site Number 8400003
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Investigational Site Number 8400001
  • Utah
    • Salt Lake City, Utah, United States, 84121
      • Investigational Site Number 8400002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Aged 6 months to <9 years or >=18 years on the day of first study vaccination (study product administration).
• For participants 6 to <12 months of age, born at full term of pregnancy (>=37 weeks) and with a birth weight >=2.5 kilograms (kg) (5.5 pounds [lbs.]).
• Informed consent form (ICF) had been signed and dated by participants >=18 years of age.
• Assent form had been signed and dated by participants 7 to <9 years of age, and ICF had been signed and dated by parent(s) or guardian(s) for participants 6 months to <9 years of age.
• Participants and parent/guardian (of participants 6 months to <9 years of age) were able to attend all scheduled visits and to comply with all study procedures.

Exclusion criteria:

• Participant was pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination and until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche, or post-menopausal for at least 1 year, or surgically sterile.
• Participation at the time of study enrollment (or in the 30 days 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.
• Receipt of any vaccine in the 30 days preceding the first study vaccination, or planned receipt of any vaccine before Visit 2 for participants who received 1 dose of influenza vaccine or Visit 3 for participants who received 2 doses of influenza vaccine.
• Previous vaccination against influenza (in the 2018-2019 influenza season) with either study vaccine or another vaccine.
• Receipt of immune globulins, blood, or blood-derived products in the 3 months preceding planned inclusion.
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the 6 months preceding planned inclusion; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the 3 months preceding planned inclusion).
• Known systemic hypersensitivity to any of the vaccine components, or history of a life- threatening reaction to study vaccine or to a vaccine containing any of the same substances.
• Thrombocytopenia, which might 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.
• Current alcohol abuse or drug addiction.
• 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 planned vaccination or febrile illness (temperature >=100.4 degree Fahrenheit [38.0 degree Celsius]). A prospective participant was not included in the study until the condition had resolved or the febrile event had subsided.
• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study (participants >=18 years of age) or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study (all participants).
• History of serious adverse reaction 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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fluzone Quadrivalent vaccine Group 1: 6 to <36 months; Participants (aged 6 to <36 months) received a 0.25-milliliter (mL) dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Biological: Fluzone Quadrivalent vaccine, 2018-2019 formulation; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
EXPERIMENTAL: Fluzone Quadrivalent vaccine Group 2: 3 to <9 years; Participants (aged 3 to <9 years) received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Biological: Fluzone Quadrivalent vaccine, 2018-2019 formulation; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
EXPERIMENTAL: Fluzone Quadrivalent vaccine Group 3: 18 to <65 years; Participants (aged 18 to <65 years) received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0.	Biological: Fluzone Quadrivalent vaccine, 2018-2019 formulation; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
EXPERIMENTAL: Flublok Quadrivalent vaccine Group 4: 18 to <65 years; Participants (aged 18 to <65 years) received a 0.5-mL dose of Flublok Quadrivalent vaccine, intramuscularly, at Day 0.	Biological: Flublok Quadrivalent vaccine, 2018-2019 formulation; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular
EXPERIMENTAL: Fluzone High-Dose vaccine Group 5: >=65 years; Participants (aged >=65 years) received a 0.5-mL dose of Fluzone High-Dose vaccine, intramuscularly, at Day 0.	Biological: Fluzone High-Dose vaccine, 2018-2019 formulation; Pharmaceutical form: Suspension for injection Route of administration: Intramuscular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants (Group 1: Aged 6 to <36 Months) Reporting Solicited Injection Site Reactions and Systemic Reactions	A solicited reaction was an adverse event (AE) that was pre-listed in the electronic case report form (eCRF) and considered to be related to vaccination. Solicited injection (Inj.) site reactions: tenderness, erythema and swelling. Solicited systemic reactions: fever, vomiting, crying abnormal, drowsiness, appetite lost and irritability.	Within 7 days post any vaccination
Number of Participants (Groups 2, 3, 4 and 5: Children Aged 3 to <9 Years and Adults 18 to >=65 Years) Reporting Solicited Injection Site Reactions or Systemic Reactions	A solicited reaction was an AE that was pre-listed in the eCRF and considered to be related to vaccination. Solicited injection site reactions: pain, erythema and swelling. Solicited systemic reactions: fever, headache, malaise, and myalgia.	Within 7 days post any vaccination
Geometric Mean Titers (GMTs) of Antibodies in Children 6 Months to <9 Years of Age (Groups 1 and 2) Receiving Fluzone Quadrivalent Vaccine	GMT of anti-influenza antibodies were measured using a hemagglutination inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage.	28 days post-final vaccination
Geometric Mean Titers of Antibodies in Adults (Groups 3, 4 and 5) Receiving Either Fluzone Quadrivalent Vaccine, Flublok Quadrivalent Vaccine, or Fluzone High-Dose Vaccine	GMTs of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage in Groups 3 and 4, and using HAI assay for 3 strains: A/H1N1, A/H3N2 and B Victoria lineage in Group 5.	Day 21 (post-vaccination)
Geometric Mean Titer Ratios (GMTRs) of Antibodies in Children 6 Months to <9 Years of Age (Groups 1 and 2) Receiving Fluzone Quadrivalent Vaccine	GMT of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. GMTRs were calculated as the ratio of GMTs post-final vaccination and pre-vaccination.	Day 0 (pre-vaccination), 28 days post-final vaccination
Geometric Mean Titer Ratios of Antibodies in Adults (Groups 3, 4 and 5) Receiving Either Fluzone Quadrivalent Vaccine, Flublok Quadrivalent Vaccine, or Fluzone High-Dose Vaccine	GMTs of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage in Groups 3 and 4, and using HAI assay for 3 strains: A/H1N1, A/H3N2 and B Victoria lineage in Group 5. GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination.	Day 0 (pre-vaccination), Day 21 (post-vaccination)
Percentage of Participants With Seroprotection to Influenza Vaccine Antigens After Vaccination With Fluzone Quadrivalent Vaccine: Groups 1 and 2	Anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. Seroprotection was defined as antibody titer >=40 (1/ dilution) at pre-vaccination and at post-final vaccination.	28 days post-final vaccination
Percentage of Participants With Seroprotection to Influenza Vaccine Antigens After Vaccination With Either Fluzone Quadrivalent Vaccine, Flublok Quadrivalent Vaccine or Fluzone High Dose Vaccine: Group 3, 4 and 5	Anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage in Groups 3 and 4, and using HAI assay for 3 strains: A/H1N1, A/H3N2 and B Victoria lineage in Group 5. Seroprotection was defined as antibody titer >=40 (1/dilution) at pre-vaccination and at post-final vaccination.	Day 21 (post-vaccination)
Percentage of Participants With Seroconversion to Influenza Vaccine Antigens After Vaccination With Fluzone Quadrivalent Vaccine: Group 1 and 2	Anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. Seroconversion was defined as either a pre-vaccination titer <10 (1/dilution) and a post-final vaccination titer >= 40 (1/dilution) or a pre-vaccination titer >= 10 (1/dilution) and >=4-fold increase in post-final vaccination titer.	28 days post-final vaccination
Percentage of Participants With Seroconversion to Influenza Vaccine Antigens After Vaccination With Either Fluzone Quadrivalent Vaccine, Flublok Quadrivalent Vaccine or Fluzone High Dose Vaccine: Group 3, 4 and 5	Anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage in Group 3 and 4, and using an HAI assay for 3 strains: A/H1N1, A/H3N2, and B Victoria lineage in Group 5. Seroconversion was defined as either a pre-vaccination titer <10 (1/dilution) and a post-vaccination titer >= 40 (1/dilution) or a pre-vaccination titer >= 10 (1/dilution) and >=4-fold increase in post-vaccination titer.	Day 21 (post-vaccination)

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 10, 2018
• Primary Completion (ACTUAL): November 12, 2018
• Study Completion (ACTUAL): November 12, 2018

Study Registration Dates

• First Submitted: July 25, 2018
• First Submitted That Met QC Criteria: July 31, 2018
• First Posted (ACTUAL): August 6, 2018

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

• 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: GRC90; U1111-1211-4864 (OTHER: UTN)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No