Influenza
Conditions
Keywords
Influenza, Influenza Virus Vaccine, Fluzone® 2011-2012 Formulation, Fluzone® High-Dose 2011-2012 Formulation, Trivalent Inactivated Influenza Vaccine
Brief summary
The aim of the study is to evaluate the safety and immunogenicity of the 2011-2012 formulation of Fluzone and Fluzone High-Dose vaccines in participants aged 65 years and older. Objectives: * To describe the safety of Fluzone vaccine and Fluzone High-Dose vaccine among adults ≥ 65 years of age. * To describe the immunogenicity of Fluzone vaccine and Fluzone High-Dose vaccine among adults ≥ 65 years of age.
Detailed description
Historically, the annual safety and immunogenicity study of Fluzone vaccine has been conducted in the US in support of licenses held by sanofi pasteur in various countries. Participants will be randomized to receive a dose of either Fluzone® or Fluzone® High-Dose vaccine and will be followed up for safety and immunogenicity. The duration of participation in the trial will be approximately 1 month.
Interventions
BIOLOGICALInfluenza Virus Vaccine: Fluzone® 2011-2012 Formulation
0.5 mL, Intramuscular
BIOLOGICALInfluenza Virus Vaccine: Fluzone® High-Dose 2011-2012 Formulation
0.5 mL, Intramuscular
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subject is ≥ 65 years of age on the day of inclusion. * Informed consent form (ICF) 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 the 2nd visit. * 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. * Influenza vaccination in the 6 months preceding enrollment in the study. * Known systemic hypersensitivity to eggs, chicken proteins, latex, or any of the vaccine components, or a history of a life-threatening reaction to Fluzone 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 Investigator's Brochure and/or the package insert) . * Receipt of immune globulins, blood, or blood-derived products in the past 3 months. * Thrombocytopenia, which may be a contraindication for intramuscular (IM) vaccination, at the discretion of the Investigator. * Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, which may be a contraindication for IM vaccination, at the discretion of the Investigator. * 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 ≥ 38.0°C \[≥ 100.4°F\]) 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Day 0 to up to Day 28 post-vaccination | Solicited injection site reactions: Pain, Erythema and Swelling. Solicited systemic reactions: Fever (temperature), Headache, Malaise, and Myalgia. Grade 3 solicited reactions were defined as: Fever ≥ 39.0°C; Pain, Headache, Malaise and Myalgia, significant, prevents daily activities; Erythema and Swelling \> 100 mm. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | Day 21 post-vaccination | Anti-influenza antibodies were measured using a hemagglutination inhibition (HAI) assay. |
| Number of Participants With Seroconversion Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine | Day 21 post-vaccination | Anti-influenza antibodies were measured using a hemagglutination inhibition (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 four-fold increase in post-vaccination titer. |
| Geometric Mean of Titer Ratios (GMTR) of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | Day 21 post-vaccination | Anti-influenza antibodies were measured using a hemagglutination inhibition (HAI) assay. Geometric mean of titer ratio is the geometric mean of the individual post-vaccination/pre-vaccination titer ratios. |
Countries
United States
Participant flow
Recruitment details
Study participants were enrolled from 07 September through 24 October 2011 in 6 clinic sites in the US.
Pre-assignment details
A total of 300 participants who met the inclusion, but no exclusion criteria were enrolled and vaccinated.
Participants by arm
| Arm | Count |
|---|---|
| Fluzone® Vaccine Group Participants received the Influenza Virus Vaccine: Fluzone® 2011-2012 Formulation. | 150 |
| Fluzone® High-Dose Vaccine Group Participants received the Influenza Virus Vaccine: Fluzone® High-Dose 2011-2012 Formulation. | 150 |
| Total | 300 |
Baseline characteristics
| Characteristic | Fluzone® High-Dose Vaccine Group | Fluzone® Vaccine Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 150 Participants | 150 Participants | 300 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 71.6 Months STANDARD_DEVIATION 4.8 | 72.6 Months STANDARD_DEVIATION 5.8 | 72.1 Months STANDARD_DEVIATION 5.3 |
| Region of Enrollment United States | 150 Participants | 150 Participants | 300 Participants |
| Sex: Female, Male Female | 92 Participants | 91 Participants | 183 Participants |
| Sex: Female, Male Male | 58 Participants | 59 Participants | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 150 | 79 / 150 |
| serious Total, serious adverse events | 1 / 150 | 0 / 150 |
Outcome results
Primary
Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine
Solicited injection site reactions: Pain, Erythema and Swelling. Solicited systemic reactions: Fever (temperature), Headache, Malaise, and Myalgia. Grade 3 solicited reactions were defined as: Fever ≥ 39.0°C; Pain, Headache, Malaise and Myalgia, significant, prevents daily activities; Erythema and Swelling \> 100 mm.
Time frame: Day 0 to up to Day 28 post-vaccination
Population: Solicited injection site and systemic reactions were assessed in all enrolled and vaccinated participants, Intent-to-treat population (Safety Analysis Set).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any injection site Pain | 36 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 injection site Pain | 1 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any injection site Erythema | 7 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 injection site Erythema | 0 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any injection site Swelling | 4 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 injection site Swelling | 0 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any Fever | 2 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 Fever | 0 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any Headache | 26 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 Headache | 2 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any Malaise | 21 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 Malaise | 5 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any Myalgia | 25 Participants |
| Fluzone® Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 Myalgia | 3 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any Malaise | 24 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any injection site Pain | 79 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 Fever | 0 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 injection site Pain | 0 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any Myalgia | 44 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any injection site Erythema | 13 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any Headache | 25 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 injection site Erythema | 2 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 Malaise | 0 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any injection site Swelling | 10 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 Headache | 0 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 injection site Swelling | 0 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Grade 3 Myalgia | 1 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Following Vaccination With One Dose of Either Fluzone® or Fluzone® High-Dose Vaccine | Any Fever | 1 Participants |
Other Pre-specified
Geometric Mean of Titer Ratios (GMTR) of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine.
Anti-influenza antibodies were measured using a hemagglutination inhibition (HAI) assay. Geometric mean of titer ratio is the geometric mean of the individual post-vaccination/pre-vaccination titer ratios.
Time frame: Day 21 post-vaccination
Population: Geometric mean of titer ratios of antibodies against Influenza vaccine antigens were determined in all enrolled and vaccinated participants, per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Fluzone® Vaccine Group | Geometric Mean of Titer Ratios (GMTR) of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | A/H1N1 (N = 147, 144) | 3.28 Titers |
| Fluzone® Vaccine Group | Geometric Mean of Titer Ratios (GMTR) of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | A/H3N2 (N = 147, 145) | 3.5 Titers |
| Fluzone® Vaccine Group | Geometric Mean of Titer Ratios (GMTR) of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | B (N = 147, 145) | 2.13 Titers |
| Fluzone® High-Dose Vaccine Group | Geometric Mean of Titer Ratios (GMTR) of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | A/H1N1 (N = 147, 144) | 7.14 Titers |
| Fluzone® High-Dose Vaccine Group | Geometric Mean of Titer Ratios (GMTR) of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | A/H3N2 (N = 147, 145) | 8.23 Titers |
| Fluzone® High-Dose Vaccine Group | Geometric Mean of Titer Ratios (GMTR) of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | B (N = 147, 145) | 3.14 Titers |
Other Pre-specified
Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine.
Anti-influenza antibodies were measured using a hemagglutination inhibition (HAI) assay.
Time frame: Day 21 post-vaccination
Population: GMTs of antibodies against Influenza vaccine antigens were determined in all enrolled and vaccinated participants, per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Fluzone® Vaccine Group | Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | A/H1N1 (Pre-vaccination; N = 147, 145) | 63.9 Titers |
| Fluzone® Vaccine Group | Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | A/H1N1 (Post-vaccination; N = 147, 144) | 228 Titers |
| Fluzone® Vaccine Group | Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | A/H3N2 (Pre-vaccination; N = 147, 145) | 104 Titers |
| Fluzone® Vaccine Group | Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | A/H3N2 (Post-vaccination; N = 147, 145) | 384 Titers |
| Fluzone® Vaccine Group | Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | B (Pre-vaccination; N = 147, 145) | 32.4 Titers |
| Fluzone® Vaccine Group | Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | B (Post-vaccination; N = 147, 145) | 73.0 Titers |
| Fluzone® High-Dose Vaccine Group | Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | B (Pre-vaccination; N = 147, 145) | 31.1 Titers |
| Fluzone® High-Dose Vaccine Group | Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | A/H1N1 (Pre-vaccination; N = 147, 145) | 57.5 Titers |
| Fluzone® High-Dose Vaccine Group | Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | A/H3N2 (Post-vaccination; N = 147, 145) | 880 Titers |
| Fluzone® High-Dose Vaccine Group | Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | A/H1N1 (Post-vaccination; N = 147, 144) | 442 Titers |
| Fluzone® High-Dose Vaccine Group | Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | B (Post-vaccination; N = 147, 145) | 106 Titers |
| Fluzone® High-Dose Vaccine Group | Geometric Mean Titers of Antibodies to Vaccine Antigens Before and Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine. | A/H3N2 (Pre-vaccination; N = 147, 145) | 102 Titers |
Other Pre-specified
Number of Participants With Seroconversion Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine
Anti-influenza antibodies were measured using a hemagglutination inhibition (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 four-fold increase in post-vaccination titer.
Time frame: Day 21 post-vaccination
Population: Seroconversion to Influenza vaccine antigens were determined in all enrolled and vaccinated participants, per-protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluzone® Vaccine Group | Number of Participants With Seroconversion Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine | A/H1N1 (N = 147, 144) | 53 Participants |
| Fluzone® Vaccine Group | Number of Participants With Seroconversion Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine | A/H3N2 (N = 147, 145) | 60 Participants |
| Fluzone® Vaccine Group | Number of Participants With Seroconversion Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine | B (N = 147, 145) | 32 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants With Seroconversion Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine | A/H1N1 (N = 147, 144) | 88 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants With Seroconversion Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine | A/H3N2 (N = 147, 145) | 100 Participants |
| Fluzone® High-Dose Vaccine Group | Number of Participants With Seroconversion Following Vaccination With Either Fluzone® or Fluzone® High-Dose Vaccine | B (N = 147, 145) | 60 Participants |