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

Phase 4

Completed

Conditions: Influenza

Interventions: Biological: Fluzone® Intradermal, Influenza Virus Vaccine (2013-2014 formulation),
Biological: Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation),
Biological: Fluzone® High-Dose, Influenza Virus Vaccine (2013-2014 formulation)

Registration Number: NCT01946438

Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary: The aim of the study is describe the safety and immunogenicity of Fluzone Quadrivalent and Fluzone Intradermal vaccines in adults 18 to \< 65 years of age, and to describe the safety and immunogenicity of Fluzone Quadrivalent and Fluzone High-Dose vaccines in adults ≥ 65 years of age.

Primary Objective:

* To describe the safety of the 2013-2014 formulations of Fluzone Quadrivalent and Fluzone Intradermal vaccines in adults 18 to \< 65 years of age and the safety of the 2013-2014 formulations of Fluzone Quadrivalent and Fluzone High-Dose vaccines in adults ≥ 65 years of age.

Observational objectives:

* To describe the immunogenicity of the 2013-2014 formulations of Fluzone Quadrivalent and Fluzone Intradermal vaccines in adults 18 to \< 65 years of age and the immunogenicity of the 2013-2014 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, 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) CPMP/BWP/214/96.

* To submit sera from selected subjects to the 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: Participants 18 to \< 65 years of age on enrollment will be randomized to receive either Fluzone Quadrivalent or Fluzone Intradermal vaccine. Participants ≥ 65 years of age at enrollment will be randomized to receive either Fluzone Quadrivalent or Fluzone High-Dose vaccine.

Solicited adverse event (AE) information will be collected for 7 days after each vaccination, unsolicited AE and Serious adverse event information will be collected from Visit 1 to Visit 2. Total duration of participation in the study is approximately 21 days.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 208

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 2013-2014 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, 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 pre-menarche or 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 (HIV), 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 the 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 the Investigator or employee with direct involvement in the proposed study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Adult Fluzone® Intradermal, Influenza Vaccine (Group 2)	Fluzone® Intradermal, Influenza Virus Vaccine (2013-2014 formulation),	Participants age 18 to \< 65 years randomized to receive a dose of Fluzone® Intradermal, Influenza Virus Vaccine (2013-2014 formulation)
Adult Fluzone® Quadrivalent, Influenza Vaccine (Group 1)	Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation),	Participants age 18 to \< 65 years randomized to receive a dose of Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation)
Elderly Fluzone® High-Dose, Influenza Vaccine (Group 4)	Fluzone® High-Dose, Influenza Virus Vaccine (2013-2014 formulation)	Participants age ≥ 65 years randomized to receive a dose of Fluzone® High-Dose, Influenza Virus Vaccine (2013-2014 formulation)
Elderly Fluzone® Quadrivalent, Influenza Vaccine (Group 3)	Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation),	Participants age ≥ 65 years randomized to receive a dose of Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation)

Primary Outcome Measures

Name	Time	Method
Number of Participants Reporting Solicited Injection-Site and Solicited Systemic Reactions Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Fluzone® Intradermal, or Fluzone® High-Dose Vaccine.	Day 0 up to Day 21 post-vaccination	Solicited injection-site reactions: Pain, Erythema, Swelling, Induration, and Ecchymosis. Systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Shivering. Grade 3: Pain, Significant, prevents daily activity; Erythema, Swelling, Induration, and Ecchymosis, \>100 mm; Fever, ≥102.1°F; Headache, Malaise, Myalgia, and Shivering, Significant, prevents daily activity.

Secondary Outcome Measures

Name	Time	Method
Geometric Mean Titers (GMTs) of Antibodies to the Antigens Contained in the 2013-2014 Formulation of Fluzone® Quadrivalent, Fluzone® Intradermal, or Fluzone® High-Dose Vaccine Before and Following Vaccination With the Respective Vaccine	Day 0 (pre-vaccination) and Day 21 after vaccination	Influenza virus antibodies were measured using a hemagglutination inhibition (HAI) assay.
Number of Participants With Seroprotection Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Fluzone® Intradermal, or Fluzone® High-Dose Vaccine	Day 0 (pre-vaccination) and Day 21 after vaccination	Influenza virus antibodies were measured using an HAI assay. Seroprotection was defined as a titer of ≥40 (1/dilution).
Number of Participants Achieving Seroconversion Following Vaccination With the 2013-2014 Formulations of Fluzone® Quadrivalent, Fluzone® Intradermal, or Fluzone® High-Dose Vaccine	Day 0 (pre-vaccination) and Day 21 after vaccination	Influenza virus antibodies were measured using an HAI assay. Seroconversion was defined as either a pre-vaccination HAI titer \< 1:10 and a post-vaccination titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and a ≥ 4-fold increase in titer after vaccination.
Geometric Mean Titer Ratios (GMTRs) of Antibodies to Antigens Contained in the 2013-2014 Formulation of Fluzone® Quadrivalent, Fluzone® Intradermal, or Fluzone® High-Dose Vaccine Following Vaccination With the Respective Vaccine	Day 21 after vaccination	Influenza virus antibodies were measured using an HAI assay. Geometric mean titer ratios are the geometric means of the individual post-vaccination/pre-vaccination titer ratios for each hemagglutinin antigen contained in the vaccines.