Safety and Immunogenicity of Fluzone® Quadrivalent and Fluzone® High-Dose, Influenza Vaccines, 2016-2017 Formulations

Study Overview
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Brief Summary
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The aim of the study was to describe the safety and immunogenicity of the 2016-2017 formulations of Fluzone Quadrivalent vaccine in children 3 to < 9 years of age and in adults 18 to < 65 years or age, and of the 2016-2017 formulation of Fluzone High-Dose vaccine in adults ≥65 years of age. Primary Observational Objectives To describe the safety of the 2016-2017 formulation of Fluzone Quadrivalent vaccine in children 3 to < 9 years of age and adults 18 to < 65 years of age, and the safety of the 2016-2017 formulation of Fluzone High-Dose vaccine in adults ≥ 65 years of age. Observational Objectives: To describe the immunogenicity of the 2016-2017 formulation of Fluzone Quadrivalent vaccine in children 3 to < 9 years of age and adults 18 to < 65 years of age, and the immunogenicity of the 2016-2017 formulation of Fluzone High-Dose vaccine in adults ≥ 65 years of age. To submit available sera from approximately 90 participants (30 participants 3 to < 9 years of age and 30 participants 18 to < 65 years of age who receive Fluzone Quadrivalent vaccine, and 30 participants ≥ 65 years of age who receive Fluzone High-Dose vaccine) to Center for Biologics Evaluation and Research (CBER) for further analysis by the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA) to support formulation recommendations for subsequent influenza vaccines.

Detailed Description
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All participants received a 0.5-mL intramuscular dose of their assigned vaccine at Visit 1. For participants 3 to < 9 years of age 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) was administered during Visit 2. Solicited adverse reaction (AR) information was collected for 7 days after vaccination. Unsolicited non-serious adverse event (AE) and serious adverse event (SAE) information was collected from Visit 1 to Visit 2 or from Visit 1 to Visit 3 for those participants receiving 2 doses of study vaccine. Immunogenicity was evaluated in all participants prior to vaccination on Day 0 (Visit 1) and after the final vaccination on Day 28 for 3 to < 9 year olds and Day 21 days for adults 18 years and older.

Official Title
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Safety and Immunogenicity of Fluzone® Quadrivalent and Fluzone® High-Dose, Influenza Vaccines, 2016-2017 Formulations

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluzone Quadrivalent vaccine, 2016-2017 formulation, No Preservative
* Biological: Fluzone Quadrivalent vaccine, 2016-2017 formulation, No Preservative
* Biological: Fluzone High-Dose, vaccine, 2016-2017 formulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 3 to <9 years or adult aged ≥ 18 years on the day of first study vaccination (study product administration) . Informed consent form 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 informed consent form (ICF) has been signed and dated by parent(s) or guardian(s) for participants 3 to <9 years of age. Participant and parent/guardian (of participants 3 to <9 years of age) were able to attend all scheduled visits and to comply with all trial 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 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 influenza 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. Current alcohol abuse or drug addiction. 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°F [38.0°C]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has 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.

Ages Eligible for Study
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Minimum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years<br>Participants aged 3 to < 9 years 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 Advisory Committee on Immunization Practices (ACIP) guidance, a second dose of Fluzone Quadrivalent vaccine was administered at Day 28. | Biological: Fluzone Quadrivalent vaccine, 2016-2017 formulation, No Preservative<br>* 0.5 mL, Intramuscular<br>* Other names: Fluzone® Quadrivalent, Influenza Vaccine;|
| Experimental: Fluzone Quadrivalent Vaccine Group 2: 18 to < 65 Years<br>Participants aged 18 to < 65 years received one 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. | Biological: Fluzone Quadrivalent vaccine, 2016-2017 formulation, No Preservative<br>* 0.5 mL, Intramuscular<br>* Other names: Fluzone® Quadrivalent, Influenza Vaccine;|
| Experimental: Fluzone High-Dose Vaccine Group 3: ≥ 65 Years<br>Participants aged ≥ 65 years received one 0.5-mL dose of Fluzone High-Dose vaccine, intramuscularly, at Day 0. | Biological: Fluzone High-Dose, vaccine, 2016-2017 formulation<br>* 0.5 mL, Intramuscular<br>* Other names: Fluzone® High-Dose Influenza Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age) | Solicited injection site reactions: Pain (Grade 1: easily tolerated, Grade 2: sufficiently discomforting to interfere with normal behavior or activities, Grade 3: incapacitating, unable to perform usual activities), erythema & swelling (Grade 1: >0 to <25 mm;Grade 2: ≥ 25 to < 50 mm; Grade 3: ≥ 50 mm). Solicited systemic reactions: Fever (Grade 1: ≥ 38.0 degrees Celsius to ≤ 38.4 degrees Celsius, Grade 2: ≥ 38.5 degrees Celsius to ≤ 38.9 degrees Celsius, Grade 3: ≥ 39.0 degrees Celsius), headache, malaise & myalgia (Grade 1: no interference with activity, Grade 2: some interference, Grade 3: significant interference). Number of participants with any solicited injection-site & systemic reactions are reported; number of participants with Grade 3 solicited injection-site & systemic reactions are also reported. | Within 7 days after any vaccination | 
| Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years) | Solicited injection site reactions: Pain (Grade 1: no interference with activity, Grade 2: some interference, Grade 3: significant; prevents daily activity), erythema & swelling (Grade 1: ≥ 25 to ≤ 50 mm; Grade 2: ≥ 51 to ≤ 100 mm; Grade 3: >100 mm). Solicited systemic reactions: Fever (Grade 1: ≥ 38.0 degrees Celsius to ≤ 38.4 degrees Celsius, Grade 2: ≥ 38.5 degrees Celsius to ≤ 38.9 degrees Celsius, Grade 3: ≥ 39.0 degrees Celsius), headache, malaise & myalgia (Grade 1: no interference with activity, Grade 2: some interference, Grade 3: significant interference). Number of participants with any solicited injection-site & systemic reactions are reported; number of participants with Grade 3 solicited injection-site & systemic reactions are also reported. | Within 7 days after any vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 1: 3 to < 9 Years) | Anti-influenza antibodies were measured using hemagglutination inhibition (HAI) assay for 4 strains: H1N1, H3N2, Victoria lineage, Yamagata lineage. | Day 0 (pre-vaccination) and 28 days post-final vaccination (post-vaccination) | 
| Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 2: 18 to < 65 Years) | Anti-influenza antibodies were measured using hemagglutination inhibition (HAI) assay for 4 strains: H1N1, H3N2, Victoria lineage, Yamagata lineage. | Day 0 (pre-vaccination) and 21 days post-final vaccination (post-vaccination) | 
| Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 3: ≥ 65 Years) | Anti-influenza antibodies were measured using hemagglutination inhibition (HAI) assay for 3 strains: H1N1, H3N2, Victoria lineage. | Day 0 (pre-vaccination) and 21 days post-final vaccination (post-vaccination) | 
| Number of Participants With Seroprotection to Influenza Vaccine Antigens (Group 1: 3 to < 9 Years) | Anti-influenza antibodies were measured using HAI assay for 4 strains: H1N1, H3N2, Victoria lineage, Yamagata lineage. Seroprotection was defined as an antibody titer ≥40 (1/dilution [dil]) at pre-vaccination and at post-final vaccination. | Day 0 (pre-vaccination) and 28 days post-final vaccination (post-vaccination) | 
| Number of Participants With Seroprotection to Influenza Vaccine Antigens (Group 2: 18 to < 65 Years) | Anti-influenza antibodies were measured using HAI assay for 4 strains: H1N1, H3N2, Victoria lineage, Yamagata lineage. Seroprotection was defined as an antibody titer ≥ 40 (1/dilution [dil]) at pre-vaccination and at post-final vaccination. | Day 0 (pre-vaccination) and 21 days post-final vaccination (post-vaccination) | 
| Number of Participants With Seroprotection to Influenza Vaccine Antigens (Group 3: ≥ 65 Years) | Anti-influenza antibodies were measured using HAI assay for 3 strains: H1N1, H3N2, Victoria lineage. Seroprotection was defined as an antibody titer ≥ 40 (1/dilution [dil]) at pre-vaccination and at post-final vaccination. | Day 0 (pre-vaccination) and 21 days post-final vaccination (post-vaccination) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Fluzone® Quadrivalent, Influenza Vaccine (2016-2017 formulation), Fluzone® High-Dose, Influenza Vaccine (2016-2017 formulation)