Immunogenicity of High-dose Inactivated, Split-virion Influenza Vaccine Versus Standard Fluzone Vaccine in the Elderly
Condition: Orthomyxoviridae Infection; Influenza; Myxovirus Infection
MeSH terms: Infections; Communicable Diseases; Influenza, Human; Orthomyxoviridae Infections
Intervention: High-Dose Inactivated, Split-Virion Influenza Vaccine; High-Dose Inactivated, Split-Virion Influenza Vaccine; High-Dose Inactivated, Split-Virion Influenza Vaccine; Inactivated, Split-Virion Influenza Vaccine
Intervention description: 0.5 mL, IM; 0.5 mL, IM; 0.5 mL, IM; 0.5 mL, IM
Intervention MeSH terms: Vaccines
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 3851.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Influenza; Orthomyxoviruses; Inactivated Split-virion influenza vaccine; Adults

Summary:

      Compared to young adults, the elderly mount a lower antibody response to vaccination. Thus,
      improvement of the immune response to influenza vaccination in this age group, which is at
      higher risk for influenza-related morbidity and mortality, represents an important unmet
      need.

      Primary Objectives:

      Immunogenicity:

        -  To demonstrate lot consistency of the Fluzone High Dose (Fluzone HD) manufacturing
           process through evaluation of the immune responses elicited by three different lots.

        -  To demonstrate the superiority of Fluzone HD vaccine compared to standard-dose Fluzone®
           vaccine.

      Secondary Objectives:

      Immunogenicity:

        -  To describe the seroprotection of Fluzone HD compared to that of standard dose Fluzone®
           vaccine.

      Safety:

        -  To describe the safety profile of Fluzone HD, in terms of solicited -, unsolicited
           adverse and serious adverse events post-vaccination.

        -  To describe clinical information on some additional defined criteria during the six
           months following vaccination.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged ≥ 65 years on the day of vaccination.

          -  Informed consent form signed.

          -  Medically stable. (Subjects may have underlying chronic conditions such as
             hypertension, diabetes, ischemic heart disease, or hypothyroidism, as long as their
             symptoms/signs are controlled. If they are on medication for a condition, the
             medication dose must have been stable for at least 3 weeks preceding vaccination.)

          -  Able to attend all scheduled visits and to comply with all trial procedures.

        Exclusion Criteria:

          -  Systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components,
             or a history of a life-threatening reaction to the standard-dose Fluzone® vaccine or a
             vaccine containing any of the same substances.

          -  Congenital or history of acquired immunodeficiency, or immunosuppressive therapy such
             as anti-cancer chemotherapy or radiation therapy within the preceding six months.

          -  Systemic corticosteroid therapy, as follows:

        Continuous use with a dosage equivalent to > 15 mg/day of oral prednisone for 90 days
        preceding vaccination.

        Sporadic use with a dosage equivalent to > 40 mg/day of oral prednisone for > 14
        consecutive days in the 90 days preceding vaccination.

        Note:Use of topical or inhalant corticosteroids is acceptable.

          -  Neoplastic disease or any hematologic malignancy (except localized skin or prostate
             cancer that is stable at the time of vaccination in the absence of therapy, as well as
             subjects who have a history of neoplastic disease and who have been disease-free for ≥
             5 years).

          -  Current alcohol abuse or drug addiction that in the opinion of the investigator may
             interfere with the subject's ability to comply with trial procedures.

          -  Receipt of blood or blood-derived products in the past three months.

          -  Participation in a trial of a high-dose influenza vaccine in the past 12 months.

          -  Receipt of influenza vaccine in the past six months.

          -  Receipt of any other vaccine in the past four weeks.

          -  Planned receipt of any other vaccine in the four weeks following the trial
             vaccination.

          -  Participation in another clinical trial in the past four weeks.

          -  Planned participation in another clinical trial during the present trial period.

        Note:Concomitant participation in an observational trial (not involving drugs, vaccines, or
        medical devices) is acceptable.

          -  Thrombocytopenia or bleeding disorder contraindicating intramuscular (IM) vaccination.

          -  History of Guillain-Barré syndrome.

          -  Subject deprived of freedom by an administrative or court order, or in an emergency
             setting, or hospitalized without his/her consent.

          -  An acute febrile illness (oral temperature ≥ 99.5ºF [≥ 37.5ºC]) within 24 hours prior
             to vaccination. If this contraindication exists, vaccination will be deferred until
             the participant has been afebrile for at least 24 hours.

          -  Signs and symptoms of an acute infectious respiratory illness. If this exists,
             vaccination will be deferred until the symptoms resolve.