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

• ClinicalTrials.gov Identifier: NCT01946438
• Recruitment Status: Completed
• First Posted: September 19, 2013
• Results First Posted: September 25, 2014
• Last Update Posted: September 25, 2014
• 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 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.

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation),; Biological: Fluzone® Intradermal, Influenza Virus Vaccine (2013-2014 formulation),; Biological: Fluzone® High-Dose, Influenza Virus Vaccine (2013-2014 formulation)	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 208 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity Among Adults of Fluzone® Quadrivalent, Fluzone® Intradermal, and Fluzone® High-Dose Influenza Virus Vaccines, 2013-2014 Formulations
• Study Start Date: September 2013
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: July 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Adult Fluzone® Quadrivalent, Influenza Vaccine (Group 1); Participants age 18 to < 65 years randomized to receive a dose of Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation)	Biological: Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation),; 0.5 mL, Intramuscular; Other Name: Fluzone® Quadrivalent, Influenza Virus Vaccine
Experimental: Adult Fluzone® Intradermal, Influenza Vaccine (Group 2); Participants age 18 to < 65 years randomized to receive a dose of Fluzone® Intradermal, Influenza Virus Vaccine (2013-2014 formulation)	Biological: Fluzone® Intradermal, Influenza Virus Vaccine (2013-2014 formulation),; 0.1 mL, Intradermal; Other Name: Fluzone® Intradermal, Influenza Virus Vaccine
Experimental: Elderly Fluzone® Quadrivalent, Influenza Vaccine (Group 3); Participants age ≥ 65 years randomized to receive a dose of Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation)	Biological: Fluzone® Quadrivalent, Influenza Virus Vaccine (2013-2014 formulation),; 0.5 mL, Intramuscular; Other Name: Fluzone® Quadrivalent, Influenza Virus Vaccine
Experimental: Elderly Fluzone® High-Dose, Influenza Vaccine (Group 4); Participants age ≥ 65 years randomized to receive a dose of Fluzone® High-Dose, Influenza Virus Vaccine (2013-2014 formulation)	Biological: Fluzone® High-Dose, Influenza Virus Vaccine (2013-2014 formulation); 0.5 mL, Intramuscular; Other Name: Fluzone® High-Dose, Influenza Virus Vaccine

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 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 :

1. 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 [ Time Frame: Day 0 (pre-vaccination) and Day 21 after vaccination ]
   Influenza virus antibodies were measured using a hemagglutination inhibition (HAI) assay.
2. Number of Participants With Seroprotection Before and Following Vaccination With the 2013-2014 Formulation of Fluzone® Quadrivalent, Fluzone® Intradermal, or Fluzone® High-Dose Vaccine [ Time Frame: 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).
3. Number of Participants Achieving Seroconversion Following Vaccination With the 2013-2014 Formulations of Fluzone® Quadrivalent, Fluzone® Intradermal, or Fluzone® High-Dose Vaccine [ Time Frame: 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.
4. 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 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, California

Santa Rosa, California, United States, 95405

United States, Iowa

Council Bluffs, Iowa, United States, 51503

United States, Louisiana

Metairie, Louisiana, United States, 70006

United States, Ohio

Cincinnati, Ohio, United States, 45249

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director; Sanofi Pasteur Inc.

More Information

Additional Information:

Related Info 

Related Info 

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01946438
• Other Study ID Numbers: GRC52; U1111-1127-7587 ( Other Identifier: WHO )
• First Posted: September 19, 2013
• Results First Posted: September 25, 2014
• Last Update Posted: September 25, 2014
• Last Verified: September 2014

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

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

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