Influenza, Myxovirus Infection, Orthomyxoviridae Infection
Conditions
Keywords
Influenza, Orthomyxoviruses, Inactivated Split-virion influenza vaccine, Adults
Brief 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.
Interventions
BIOLOGICALHigh-Dose Inactivated, Split-Virion Influenza Vaccine
0.5 mL, IM
0.5 mL, IM
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | Day 0 and Day 28 Post-vaccination | Antibodies against each of three Influenza antigens (virus) in Fluzone® High-Dose and Standard Fluzone® vaccines (A/H1N1 New-Caledonia; A/H3N2 Wisconsin; and B Malaysia) were determined by the Hemagglutination inhibition assay method. |
| Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | Day 28 Post-vaccination | Seroconversion was defined as a Hemagglutination Inhibition Antibody Titers of Titer ≥40 (1/dil) on Day 28 if pre-vaccination (Day 0) titer \<10 (1/dil); or a four-fold increase of titer on Day 28, if pre-vaccination (Day 0) titer is ≥10 (1/dil) for each of the three Influenza vaccine antigens (A/H1N1 New-Caledonia; A/H3N2 Wisconsin; and B Malaysia). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | Day 0 and Day 28 Post-vaccination | Seroprotection was defined as a Hemagglutination Inhibition Titers of at least 40 (≥ 1:40) for each of the Influenza vaccine antigens (A/H1N1 New-Caledonia; A/H3N2 Wisconsin; and B Malaysia) pre- or post-vaccination with Fluzone® High-Dose or Standard Fluzone® vaccines. |
| Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Day 0 to Day 7 Post-vaccination | The occurrence, time to onset, number of days of occurrence, and severity of solicited injection site reactions: Injection Site Pain, Erythema, and Swelling; Solicited systemic reactions: Fever (temperature), Headache, Malaise, and Myalgia were collected. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled from 09 October 2006 to 21 December 2006 at 30 US sites.
Pre-assignment details
A total of 3851 participants who met the inclusion and exclusion criteria were randomized and vaccinated. The vaccine received by 14 participants could not be verified, they were excluded from all analyses except immunogenicity analysis. 4 participants that started the study, but had no post-vaccination assessment were also excluded from analysis.
Participants by arm
| Arm | Count |
|---|---|
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 Participants aged 65 years or older at enrollment, treated with high-dose trivalent inactivated influenza vaccine (Fluzone HD) 2006-2007 formulation, Lot 1 | 855 |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 Participants aged 65 years or older at enrollment, treated with high-dose trivalent inactivated influenza vaccine (Fluzone HD) 2006-2007 formulation, Lot 2 | 848 |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 Participants aged 65 years or older at enrollment, treated with high-dose trivalent inactivated influenza vaccine (Fluzone HD) 2006-2007 formulation, Lot 3 | 870 |
| Active Comparator (Standard Fluzone®) Participants aged 65 years or older at enrollment, treated with standard Fluzone® vaccine 2006-2007 formulation | 1,260 |
| Total | 3,833 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 5 |
| Overall Study | Protocol Violation | 2 | 0 | 0 | 0 |
| Overall Study | Serious Adverse Events | 1 | 0 | 1 | 4 |
| Overall Study | Withdrawal by Subject | 5 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Active Comparator (Standard Fluzone®) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 848 Participants | 870 Participants | 855 Participants | 1260 Participants | 3833 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 72.9 Years STANDARD_DEVIATION 6.2 | 72.9 Years STANDARD_DEVIATION 6.17 | 72.9 Years STANDARD_DEVIATION 6.15 | 72.9 Years STANDARD_DEVIATION 5.99 | 72.9 Years STANDARD_DEVIATION 6.17 |
| Region of Enrollment United States | 848 participants | 870 participants | 855 participants | 1260 participants | 3833 participants |
| Sex: Female, Male Female | 438 Participants | 445 Participants | 437 Participants | 688 Participants | 2008 Participants |
| Sex: Female, Male Male | 410 Participants | 425 Participants | 418 Participants | 572 Participants | 1825 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 455 / 855 | 454 / 848 | 449 / 870 | 544 / 1,260 |
| serious Total, serious adverse events | 56 / 855 | 56 / 848 | 44 / 870 | 93 / 1,260 |
Outcome results
Primary
Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines.
Antibodies against each of three Influenza antigens (virus) in Fluzone® High-Dose and Standard Fluzone® vaccines (A/H1N1 New-Caledonia; A/H3N2 Wisconsin; and B Malaysia) were determined by the Hemagglutination inhibition assay method.
Time frame: Day 0 and Day 28 Post-vaccination
Population: The geometric mean titers was assessed in the Full Analysis Set according to the vaccine the subjects were randomized to receive. A total of 3851 participants were included in this analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Pre-Dose | 28.25 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Post-Dose | 112.77 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Pre-Dose | 74.53 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Post-Dose | 595.03 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | B/Malaysia Pre-Dose | 19.24 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | B/Malaysia Post-Dose | 68.98 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | B/Malaysia Post-Dose | 69.26 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Post-Dose | 628.54 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Pre-Dose | 29.41 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Pre-Dose | 77.3 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Post-Dose | 114.63 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | B/Malaysia Pre-Dose | 18.96 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Post-Dose | 120.02 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Pre-Dose | 72.07 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Post-Dose | 603.59 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | B/Malaysia Post-Dose | 68.93 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | B/Malaysia Pre-Dose | 19.78 Titers |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Pre-Dose | 27.86 Titers |
| Active Comparator (Standard Fluzone®) | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | B/Malaysia Pre-Dose | 18.96 Titers |
| Active Comparator (Standard Fluzone®) | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | B/Malaysia Post-Dose | 52.34 Titers |
| Active Comparator (Standard Fluzone®) | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Post-Dose | 67.29 Titers |
| Active Comparator (Standard Fluzone®) | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Post-Dose | 332.46 Titers |
| Active Comparator (Standard Fluzone®) | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Pre-Dose | 29.36 Titers |
| Active Comparator (Standard Fluzone®) | Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Pre-Dose | 74.74 Titers |
Primary
Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines.
Seroconversion was defined as a Hemagglutination Inhibition Antibody Titers of Titer ≥40 (1/dil) on Day 28 if pre-vaccination (Day 0) titer \<10 (1/dil); or a four-fold increase of titer on Day 28, if pre-vaccination (Day 0) titer is ≥10 (1/dil) for each of the three Influenza vaccine antigens (A/H1N1 New-Caledonia; A/H3N2 Wisconsin; and B Malaysia).
Time frame: Day 28 Post-vaccination
Population: The immunogenicity analysis was performed on the Full Analysis Set according to the vaccine the subjects were randomized to receive. A total of 3851 participants were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia | 47 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | B/Malaysia | 43 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin | 70 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia | 47 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin | 68 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | B/Malaysia | 41 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | B/Malaysia | 42 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia | 52 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin | 70 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | B/Malaysia | 30 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin | 51 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia | 23 Percentage of Participants |
Secondary
Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination
The occurrence, time to onset, number of days of occurrence, and severity of solicited injection site reactions: Injection Site Pain, Erythema, and Swelling; Solicited systemic reactions: Fever (temperature), Headache, Malaise, and Myalgia were collected.
Time frame: Day 0 to Day 7 Post-vaccination
Population: The safety analysis was performed on the Full Analysis Set according to the participants who actually received a vaccine, whether or not the subject received the assigned vaccine. A total of 3,833 participants were included in the analysis set for the evaluation of all safety.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Erythema (≥ 5 cm) | 3 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Swelling | 9 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Swelling (≥ 5 cm) | 1 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Erythema | 16 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Solicited Injection Site Reaction | 41 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Pain | 35 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Pain (Incapacitating) | 1 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Solicited Systemic Reaction | 37 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Fever | 4 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Fever (>102.2 ºF or >39.0 ºC) | 0 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Headache | 17 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Headache (Prevents Daily Activities) | 1 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Malaise | 20 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Malaise (Prevents Daily Activities) | 1 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Myalgia | 23 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Myalgia (Prevents Daily Activities) | 1 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Pain | 34 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Fever | 3 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Myalgia (Prevents Daily Activities) | 1 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Headache (Prevents Daily Activities) | 2 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Myalgia | 21 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Fever (>102.2 ºF or >39.0 ºC) | 0 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Swelling (≥ 5 cm) | 2 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Headache | 16 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Erythema (≥ 5 cm) | 1 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Pain (Incapacitating) | 0 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Erythema | 15 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Swelling | 9 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Malaise | 18 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Solicited Systemic Reaction | 33 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Malaise (Prevents Daily Activities) | 2 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Solicited Injection Site Reaction | 42 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Pain | 38 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Erythema (≥ 5 cm) | 2 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Malaise (Prevents Daily Activities) | 2 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Pain (Incapacitating) | 0 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Solicited Systemic Reaction | 33 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Myalgia (Prevents Daily Activities) | 2 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Fever | 4 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Fever (>102.2 ºF or >39.0 ºC) | 0 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Myalgia | 21 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Headache | 17 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Headache (Prevents Daily Activities) | 1 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Solicited Injection Site Reaction | 43 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Swelling | 9 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Malaise | 16 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Swelling (≥ 5 cm) | 1 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Erythema | 14 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Myalgia (Prevents Daily Activities) | 0 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Solicited Systemic Reaction | 29 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Swelling (≥ 5 cm) | 1 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Solicited Injection Site Reaction | 31 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Malaise (Prevents Daily Activities) | 1 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Pain (Incapacitating) | 0 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Malaise | 14 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Swelling | 6 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Erythema (≥ 5 cm) | 1 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Fever (>102.2 ºF or >39.0 ºC) | 0 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Pain | 24 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Headache | 14 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Myalgia | 18 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Fever | 2 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Any Erythema | 11 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination | Grade 3 Headache (Prevents Daily Activities) | 0 Percentage of Participants |
Secondary
Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines.
Seroprotection was defined as a Hemagglutination Inhibition Titers of at least 40 (≥ 1:40) for each of the Influenza vaccine antigens (A/H1N1 New-Caledonia; A/H3N2 Wisconsin; and B Malaysia) pre- or post-vaccination with Fluzone® High-Dose or Standard Fluzone® vaccines.
Time frame: Day 0 and Day 28 Post-vaccination
Population: The immunogenicity analysis was performed on the Full Analysis Set according to the vaccine the subjects were randomized to receive. A total of 3851 participants were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Pre-Dose | 44 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Post-Dose | 91 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Pre-Dose | 70 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | B/Malaysia Pre-Dose | 27 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | B/Malaysia Post-Dose | 80 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Post-Dose | 99 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Post-Dose | 89 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Pre-Dose | 69 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Post-Dose | 99 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | B/Malaysia Pre-Dose | 28 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Pre-Dose | 46 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | B/Malaysia Post-Dose | 78 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Post-Dose | 99 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | B/Malaysia Pre-Dose | 30 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | B/Malaysia Post-Dose | 80 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Post-Dose | 90 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Pre-Dose | 68 Percentage of Participants |
| High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3 | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Pre-Dose | 42 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Pre-Dose | 69 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H3N2 Wisconsin Post-Dose | 97 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | B/Malaysia Post-Dose | 68 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Pre-Dose | 46 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | A/H1N1 New Caledonia Post-Dose | 77 Percentage of Participants |
| Active Comparator (Standard Fluzone®) | Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. | B/Malaysia Pre-Dose | 27 Percentage of Participants |