Study of Fluzone® Quadrivalent, Fluzone® Intradermal Quadrivalent, and Fluzone® High-Dose, Influenza Vaccines in Adults

Study Overview
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Brief Summary
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The aim of the study is to evaluate the safety and immunogenicity of the 2015-2016 formulations of Fluzone Quadrivalent and Fluzone Intradermal Quadrivalent vaccines in adults 18 to < 65 years of age, and of the 2015-2016 formulations of Fluzone Quadrivalent and Fluzone High-Dose vaccines in adults ≥ 65 years of age. Primary Objective: - To describe the safety of the 2015-2016 formulations of Fluzone Quadrivalent and Fluzone Intradermal Quadrivalent vaccines in adults 18 to < 65 years of age and the safety of the 2015-2016 formulations of Fluzone Quadrivalent and Fluzone High-Dose vaccines in adults ≥ 65 years of age. Observational Objectives: To describe the immunogenicity of the 2015-2016 formulations of Fluzone Quadrivalent and Fluzone Intradermal Quadrivalent vaccines in adults 18 to < 65 years of age and the immunogenicity of the 2015-2016 formulations of Fluzone Quadrivalent and Fluzone High-Dose vaccines in adults ≥ 65 years of age. To evaluate the compliance, in terms of immunogenicity, of each study vaccine (Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, and Fluzone High-Dose) in the applicable age group with the historical requirements of the Committee for Human Medicinal Products (CHMP) Note for Guidance (NfG) Committee for Propriety Medicinal Products (CPMP) - CHMP NfG CPMP/BWP/214/96.

Detailed Description
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Adults age 18 to < 65 years will be randomly assigned to receive either Fluzone Quadrivalent or Fluzone Intradermal Quadrivalent vaccine and adults age ≥ 65 years will be randomly assigned to receive either Fluzone Quadrivalent or Fluzone High-Dose vaccine. All subjects will receive a single dose of their randomly assigned vaccine. They will be followed from Visit 1 to Visit 2 for evaluation of safety outcomes. Solicited adverse reactions will be collected for 7 days after vaccination. Unsolicited non-serious adverse events (AEs) and serious adverse events (SAEs) will be collected from Visit 1 to Visit 2.

Official Title
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Safety and Immunogenicity Among Adults of Fluzone® Quadrivalent, Fluzone® Intradermal Quadrivalent, and Fluzone® High-Dose, Influenza Vaccines, 2015-2016 Formulations

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluzone Quadrivalent vaccine, 2015-2016 formulation, No Preservative
* Biological: Fluzone Intradermal Quadrivalent vaccine, 2015-2016 formulation
* Biological: Fluzone Quadrivalent vaccine, 2015-2016 formulation, No Preservative
* Biological: Fluzone High-Dose vaccine, 2015-2016 formulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥ 18 years of age on the day of inclusion Informed consent form has been signed and dated Able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria: History of serious adverse reaction to any influenza vaccine Receipt of any vaccine within 30 days before receiving study vaccine, or plans to receive another vaccine before Visit 2 Participation in another interventional clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 30 days preceding the first study vaccination or during the course of the study, unless no intervention for the other study occurred within the 30 days prior to the first study vaccination and none are planned before the subject would complete safety surveillance for the present study Thrombocytopenia, which may be a contraindication for intramuscular vaccination, at the discretion of the Investigator Prior vaccination with any 2015-2016 formulation of influenza vaccine Known systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or a history of a life-threatening reaction to Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, or Fluzone High-Dose vaccine or to a vaccine containing any of the same substances (the complete list of vaccine components is included in the Prescribing Information) Receipt of immune globulins, blood, or blood-derived products in the past 3 months Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, which may be a contraindication for intramuscular vaccination, at the discretion of the Investigator Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination and until at least 4 weeks after vaccination) Any condition that in the opinion of the Investigator would pose a health risk to the subject if enrolled or could interfere with the evaluation of the vaccine Personal history of Guillain-Barré syndrome 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) Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion Seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C, as reported by the subject. Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily Current alcohol or drug addiction that, in the opinion of the Investigator, might interfere with the ability to comply with trial procedures Moderate or severe acute illness/infection (according to Investigator judgment) or febrile illness (temperature ≥ 100.4°F) on the day of vaccination. A prospective subject 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 an Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of an Investigator or employee with direct involvement in the proposed study.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group 1<br>Adults 18 to < 65 years of age randomly assigned to receive an intramuscular injection of one dose of Fluzone Quadrivalent vaccine | Biological: Fluzone Quadrivalent vaccine, 2015-2016 formulation, No Preservative<br>* 0.5 mL, Intramuscular (IM)<br>* Other names: Fluzone® Quadrivalent, Influenza Vaccine;|
| Experimental: Study Group 2<br>Adults 18 to < 65 years of age randomly assigned to receive an intradermal injection of one dose of Fluzone Intradermal Quadrivalent vaccine | Biological: Fluzone Intradermal Quadrivalent vaccine, 2015-2016 formulation<br>* 0.1 mL, Intradermal<br>* Other names: Fluzone® Intradermal Quadrivalent, Influenza Vaccine;|
| Experimental: Study Group 3<br>Adults ≥ 65 years of age randomly assigned to receive an intramuscular injection of one dose of Fluzone Quadrivalent vaccine | Biological: Fluzone Quadrivalent vaccine, 2015-2016 formulation, No Preservative<br>* 0.5 mL, Intramuscular<br>* Other names: Fluzone® Quadrivalent, Influenza Vaccine;|
| Experimental: Study Group 4<br>Adults ≥ 65 years of age randomly assigned to receive an intramuscular injection of one dose of Fluzone High-Dose vaccine | Biological: Fluzone High-Dose vaccine, 2015-2016 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 With Solicited Injection-Site or Systemic Reactions After Receipt of the 2015-2016 Formulation of Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, or Fluzone High-Dose Vaccine | Solicited injection-site reactions: Pain, Erythema, Swelling, Induration, and Ecchymosis. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Shivering. Grade 3 solicited injection-site reactions: Pain, Significant; prevents daily activity. Erythema, Swelling, Induration, and Ecchymosis >100 mm. Grade 3 solicited systemic reactions: Fever, ≥ 39.0°C or ≥ 102.1°F; Headache, Malaise, Myalgia, and Shivering, Significant; prevents daily activity. A participant (18 to < 65 Years) who was randomly assigned to receive Fluzone Intradermal Quadrivalent vaccine received Fluzone Quadrivalent vaccine instead; this participant was excluded from the Per-protocol analysis Set and was included in the Fluzone Quadrivalent vaccine Group in the Safety Analysis Set and the assigned group in the Full Analysis Set. | Day 0 up to Day 7 post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers of Influenza Antibodies Pre- and Post-Vaccination With the 2015-2016 Formulation of Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, or Fluzone High-Dose Vaccine | Anti-influenza antibodies were measured using an hemagglutination inhibition assay. | Day 0 (pre-vaccination) and 21 days post-vaccination | 
| Number of Participants Achieving Seroprotection Pre and Post-Vaccination With the 2015-2016 Formulation of Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, or Fluzone High-Dose Vaccine | Anti-influenza antibodies were measured using an hemagglutination inhibition assay. Seroprotection was defined as the number of participants with a titer ≥ 40 (1/dilution) at pre-vaccination and 21 days post-vaccination. | Day 0 (Pre-vaccination) and 21 days post-vaccination | 
| Number of Participants Achieving Seroconversion Following Vaccination With the 2015-2016 Formulation of Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, or Fluzone High-Dose Vaccine | Anti-influenza antibodies were measured using an hemagglutination inhibition assay. Seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and a ≥ 4-fold increase in titer post-vaccination. | 21 days post-vaccination | 
| Geometric Mean Titer Ratios of Influenza Antibodies Post-Vaccination With the 2015-2016 Formulation of Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, or Fluzone High-Dose Vaccine | Anti-influenza antibodies were measured using an hemagglutination inhibition assay. | 21 days 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, Fluzone® Intradermal Quadrivalent, Influenza Vaccine, Fluzone® High Dose, Influenza Vaccine