Influenza
Conditions
Keywords
Influenza
Brief summary
To describe the safety of the inactivated, split-virion influenza vaccine, 2008-2009 formulation. To evaluate the compliance, in terms of immunogenicity, of the inactivated, split-virion influenza vaccine 2008-2009 formulation with the requirements of the Committee for Human Medicinal Products (CHMP) Note for Guidance (NfG) CPMP/BWP/214/96.
Interventions
BIOLOGICALSplit, Inactivated, Trivalent Influenza vaccine (Fluzone®)
0.5 mL, intramuscular
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Participant is 18 years of age or older on the day of inclusion. * Participant willing and able to attend scheduled visits and to comply with the study procedures during the entire duration of the study. * Participant in reasonably good health as assessed by the Investigator. * Participant willing and able to give informed consent. * For a woman, inability to bear a child or negative serum/urine pregnancy test.
Exclusion criteria
* Self-reported allergy to egg proteins, chicken proteins, or one of the constituents of the vaccine, such as thimerosal or formaldehyde. * An acute illness with or without fever in the 72 hours preceding enrollment in the trial. * Clinically significant findings in vital signs (including temperature ≥ 99.5°F oral) or review of systems. * Self-reported history of severe adverse event to any influenza vaccine. * Laboratory-confirmed influenza infection or vaccination against influenza in the 6 months preceding enrollment in the study. * Any vaccination in the 14 days preceding enrollment in the study or scheduled between Visit 1 and Visit 2. * Participation in any other interventional drug or vaccine trial within the 30 days preceding or during enrollment into this study.\* * Immunocompromising condition or immunosuppressive therapy (including systemic steroid use for 2 weeks or more), cancer chemotherapy, or radiation therapy at the time of enrollment, planned during the period of this study, or at any time within the past 6 months. * Receipt of blood or blood products within the 3 months preceding enrollment in the study. * Diabetes mellitus requiring pharmacological control. * 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. * Person deprived of freedom by an administrative or court order (having legal or medical guardian). * For women of childbearing potential, a positive urine pregnancy test, breast feeding, or not using a medically approved and reliable form of contraception (oral contraceptives or double barrier method) for the duration of the trial. * Current use of alcohol or recreational drugs that may interfere with the subject's ability to comply with trial procedures. * Thrombocytopenia or bleeding disorder contraindicating intramuscular vaccination. * Prior personal history of Guillain-Barré syndrome. \* Subjects enrolled into this study will not be prohibited from donating blood for non-interventional studies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Days 0-3 post-vaccination | Solicited Injection Site Reaction: Pain, Erythema, Swelling, Induration, and Ecchymosis. Solicited Systemic Reaction: Fever (temperature), Headache, Malaise, Myalgia, and Shivering |
| Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | Day 0 and 21 days post-vaccination | — |
| Percentage of Participants With at Least 1:40 Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone® Vaccine (Seroprotection) | 21 days post-vaccination | Seroprotection was defined as post-vaccination titer value of ≥ 1:40. |
| Percentage of Participants With at Least a 4-Fold Rise in Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone Vaccine (Seroconversion) | 21 days post-vaccination | Seroconversion was defined as a four-fold rise in titers or greater from baseline. If the baseline titer value is \< 10, then 10 is used as the baseline value for the purposes of this calculation |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled from 26 August to 03 September 2008 at one US clinical center.
Pre-assignment details
A total of 122 participants who met the inclusion and exclusion criteria were enrolled. Of these, 120 participants were vaccinated.
Participants by arm
| Arm | Count |
|---|---|
| Age 18-60 Years Participants received one dose of Fluzone® vaccine on Day 0. | 59 |
| Age 61 Years and Older Participants received one dose of Fluzone® vaccine on Day 0. | 61 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Age 61 Years and Older | Age 18-60 Years | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 53 Participants | 0 Participants | 53 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 59 Participants | 67 Participants |
| Age, Continuous | 74.7 Years STANDARD_DEVIATION 7.67 | 43.2 Years STANDARD_DEVIATION 12.14 | 59.2 Years STANDARD_DEVIATION 18.74 |
| Region of Enrollment United States | 61 participants | 59 participants | 120 participants |
| Sex: Female, Male Female | 38 Participants | 45 Participants | 83 Participants |
| Sex: Female, Male Male | 23 Participants | 14 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 59 | 16 / 61 |
| serious Total, serious adverse events | 0 / 59 | 0 / 61 |
Outcome results
Primary
Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation
Time frame: Day 0 and 21 days post-vaccination
Population: Analysis of Geometric Mean Titers was in the per-protocol population. (Participants that did not provide both pre- and post- vaccination serum samples within the specified time window were excluded from analysis)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Age 18-60 Years | Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | A/Brisbane/59/2007 (H1N1) IVR-148 Pre-dose | 26.9 Titers |
| Age 18-60 Years | Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | A/Uruguay (H3N2) X-175-C Post-dose | 528.7 Titers |
| Age 18-60 Years | Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | B/Florida/04/2006 Post-dose | 84.0 Titers |
| Age 18-60 Years | Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | A/Uruguay (H3N2) X-175-C Pre-dose | 34.9 Titers |
| Age 18-60 Years | Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | B/Florida/04/2006 Pre-dose | 28.5 Titers |
| Age 18-60 Years | Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | A/Brisbane/59/2007 (H1N1) IVR-148 Post-dose | 130.9 Titers |
| Age 61 Years and Older | Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | B/Florida/04/2006 Pre-dose | 21.6 Titers |
| Age 61 Years and Older | Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | A/Uruguay (H3N2) X-175-C Pre-dose | 31.5 Titers |
| Age 61 Years and Older | Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | A/Uruguay (H3N2) X-175-C Post-dose | 300.3 Titers |
| Age 61 Years and Older | Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | A/Brisbane/59/2007 (H1N1) IVR-148 Post-dose | 46.1 Titers |
| Age 61 Years and Older | Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | B/Florida/04/2006 Post-dose | 56.2 Titers |
| Age 61 Years and Older | Geometric Mean Titers (GMTs) for the 3 Influenza Strains Pre- and Post-vaccination With Fluzone® Vaccine 2008-2009 Formulation | A/Brisbane/59/2007 (H1N1) IVR-148 Pre-dose | 16.9 Titers |
Primary
Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine.
Solicited Injection Site Reaction: Pain, Erythema, Swelling, Induration, and Ecchymosis. Solicited Systemic Reaction: Fever (temperature), Headache, Malaise, Myalgia, and Shivering
Time frame: Days 0-3 post-vaccination
Population: Safety profile was assessed in the intent-to-treat (ITT) population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Ecchymosis | 2 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Pain (Incapacitating) | 0 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Solicited Systemic Reaction | 25 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Swelling | 4 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Fever | 1 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Ecchymosis (≥ 5 cm) | 0 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Fever (> 102.2 ºF) | 0 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Swelling (≥ 5 cm) | 0 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Headache | 17 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Erythema (Redness) | 7 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Headache | 1 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Induration | 5 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Malaise | 9 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Pain | 34 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Malaise (Prevents daily activities) | 1 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Myalgia | 19 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Solicited Injection Site Reaction | 35 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Myalgia (Prevents daily activities) | 1 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Induration (≥ 5 cm) | 0 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Shivering | 4 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Erythema (Redness) | 0 Participants |
| Age 18-60 Years | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Shivering (Prevents daily activities) | 0 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Myalgia | 10 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Solicited Injection Site Reaction | 18 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Ecchymosis | 1 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Malaise (Prevents daily activities) | 0 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Shivering (Prevents daily activities) | 0 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Pain | 16 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Pain (Incapacitating) | 1 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Erythema (Redness) | 2 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Erythema (Redness) | 0 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Swelling | 1 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Swelling (≥ 5 cm) | 1 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Induration | 1 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Induration (≥ 5 cm) | 0 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Ecchymosis (≥ 5 cm) | 0 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Solicited Systemic Reaction | 14 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Fever | 0 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Fever (> 102.2 ºF) | 0 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Headache | 6 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Headache | 0 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Malaise | 2 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Grade 3 Myalgia (Prevents daily activities) | 1 Participants |
| Age 61 Years and Older | Number of Participants With at Least 1 Solicited Injection Site Solicited Systemic Reactions Post-vaccination With Fluzone® Vaccine. | Any Shivering | 0 Participants |
Primary
Percentage of Participants With at Least 1:40 Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone® Vaccine (Seroprotection)
Seroprotection was defined as post-vaccination titer value of ≥ 1:40.
Time frame: 21 days post-vaccination
Population: Analysis of seroprotection was in the per-protocol population. (Participants that did not provide both pre- and post- vaccination serum samples within the specified time window were excluded from analysis)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Age 18-60 Years | Percentage of Participants With at Least 1:40 Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone® Vaccine (Seroprotection) | A/Brisbane/59/2007 (H1N1) IVR-148 | 88 Percentage of Participants |
| Age 18-60 Years | Percentage of Participants With at Least 1:40 Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone® Vaccine (Seroprotection) | A/Uruguay (H3N2) X-175-C | 98 Percentage of Participants |
| Age 18-60 Years | Percentage of Participants With at Least 1:40 Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone® Vaccine (Seroprotection) | B/Florida/04/2006 | 82 Percentage of Participants |
| Age 61 Years and Older | Percentage of Participants With at Least 1:40 Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone® Vaccine (Seroprotection) | A/Brisbane/59/2007 (H1N1) IVR-148 | 63 Percentage of Participants |
| Age 61 Years and Older | Percentage of Participants With at Least 1:40 Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone® Vaccine (Seroprotection) | A/Uruguay (H3N2) X-175-C | 98 Percentage of Participants |
| Age 61 Years and Older | Percentage of Participants With at Least 1:40 Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone® Vaccine (Seroprotection) | B/Florida/04/2006 | 67 Percentage of Participants |
Primary
Percentage of Participants With at Least a 4-Fold Rise in Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone Vaccine (Seroconversion)
Seroconversion was defined as a four-fold rise in titers or greater from baseline. If the baseline titer value is \< 10, then 10 is used as the baseline value for the purposes of this calculation
Time frame: 21 days post-vaccination
Population: Analysis of seroconversion was in the per-protocol population. (Participants that did not provide both pre- and post- vaccination serum samples within the specified time window were excluded from analysis)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Age 18-60 Years | Percentage of Participants With at Least a 4-Fold Rise in Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone Vaccine (Seroconversion) | A/Brisbane/59/2007 (H1N1) IVR-148 | 42 Percentage of Participants |
| Age 18-60 Years | Percentage of Participants With at Least a 4-Fold Rise in Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone Vaccine (Seroconversion) | A/Uruguay (H3N2) X 175-C | 77 Percentage of Participants |
| Age 18-60 Years | Percentage of Participants With at Least a 4-Fold Rise in Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone Vaccine (Seroconversion) | B/Florida/04/2006 | 36 Percentage of Participants |
| Age 61 Years and Older | Percentage of Participants With at Least a 4-Fold Rise in Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone Vaccine (Seroconversion) | A/Brisbane/59/2007 (H1N1) IVR-148 | 33 Percentage of Participants |
| Age 61 Years and Older | Percentage of Participants With at Least a 4-Fold Rise in Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone Vaccine (Seroconversion) | A/Uruguay (H3N2) X 175-C | 84 Percentage of Participants |
| Age 61 Years and Older | Percentage of Participants With at Least a 4-Fold Rise in Hemagglutination Inhibition Antibody Titer Post-Vaccination With Fluzone Vaccine (Seroconversion) | B/Florida/04/2006 | 31 Percentage of Participants |