Influenza
Conditions
Keywords
Influenza vaccine
Brief summary
To describe the safety during Days 0 to 21 following injection of the 2005-2006 formulation of the inactivated, split-virion influenza vaccine Fluzone in subjects aged 18-59 years and subjects aged ≥ 60 years. To describe the immune response (antibodies to hemagglutinin) 21 days following injection of the 2005-2006 formulation of the inactivated, split-virion influenza vaccine Fluzone, in subjects aged 18-59 years and subjects aged ≥ 60 years. To submit remaining available sera to the Center for Biologics Evaluation and Research (CBER) for further analysis by the Food and Drug Administration (FDA), Center for Disease Control and Prevention (CDC) and the World Health Organization (WHO) to support selection and recommendation of antigen strains for subsequent influenza vaccines.
Interventions
BIOLOGICALFluzone®: Influenza Virus Vaccine
0.5 mL, Intramuscular
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Participant aged 18 years or older on the day of inclusion. * Participant able to attend scheduled visits and to comply with the study procedures during the entire duration of the study. * Participant is in reasonably good health as assessed by the investigator. * Participant willing and able to meet protocol requirements. * 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 (temperature ≥ 99.5°F oral) in the 72 hours preceding enrollment in the trial. * Clinically significant findings in vital signs (including temperature ≥ 99.5°F oral) on 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 3. * Vaccination planned in the 4 weeks following any trial vaccination. * Participation in any other interventional drug or vaccine trial within the 30 days preceding or during enrollment into this study. * Immunocompromising 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 posed a health risk to the subject if enrolled or interfered 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 form of contraception for the duration of the trial. * Current abuse of alcohol or drug addiction that interfered with the subject's ability to comply with trial procedures. * Thrombocytopenia or bleeding disorder contraindicating intramuscular (IM) vaccination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Day 0 to 3 post-vaccination | — |
| Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | 21 days post-vaccination | GMTs and their 95% Confidence Intervals are presented for each of the 3 antigens in Fluzone® vaccine (2005-2006 Formulation) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥ 40 Serum Hemagglutination Inhibition Antibody Titers Post-vaccination. | 21 Days post-vaccination | Seroprotection: Percentage of participants with ≥ 40 serum hemagglutination inhibition antibody titers 21 days post-vaccination. |
| Percentage of Participants With a ≥ 4-fold Increase in Serum Hemagglutination Inhibition Antibody Titers Post-vaccination | Day 21 post-vaccination | Seroconversion: percentage of participants with at least a 4-fold increase in serum hemagglutination inhibition antibody titers at 21 days post-vaccination. |
Countries
United States
Participant flow
Recruitment details
Study participants were enrolled from 09 September to 18 October 2005 in one medical clinic in the US
Pre-assignment details
A total of 120 subjects that met the inclusion and exclusion criteria were enrolled and vaccinated.
Participants by arm
| Arm | Count |
|---|---|
| Age 18 to 59 Years Participants aged 18 to 59 years at enrollment received 0.5 mL of Fluzone® vaccine intramuscularly. | 60 |
| Age 60 Years and Older Participants aged 60 years and older at enrollment received 0.5 mL of Fluzone® vaccine intramuscularly. | 60 |
| Total | 120 |
Baseline characteristics
| Characteristic | Age 60 Years and Older | Age 18 to 59 Years | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 58 Participants | 0 Participants | 58 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 59 Participants | 61 Participants |
| Age, Continuous | 75.7 Years STANDARD_DEVIATION 6.24 | 42.8 Years STANDARD_DEVIATION 11.25 | 59.3 Years STANDARD_DEVIATION 18.85 |
| Region of Enrollment United States | 60 participants | 60 participants | 120 participants |
| Sex: Female, Male Female | 39 Participants | 49 Participants | 88 Participants |
| Sex: Female, Male Male | 21 Participants | 11 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 60 | 5 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 |
Outcome results
Primary
Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination
GMTs and their 95% Confidence Intervals are presented for each of the 3 antigens in Fluzone® vaccine (2005-2006 Formulation)
Time frame: 21 days post-vaccination
Population: GMT results were assessed on the per-protocol population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Age 18 to 59 Years | Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | A/New Caledonia/20/99 (H1N1), Post | 153.6 Titer |
| Age 18 to 59 Years | Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | A/New York/55/2004 (H3N2), Pre | 23.9 Titer |
| Age 18 to 59 Years | Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | A/New York/55/2004 (H3N2), Post | 341.0 Titer |
| Age 18 to 59 Years | Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | B/Jiangsu/10/2003, Pre | 25.9 Titer |
| Age 18 to 59 Years | Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | B/Jiangsu/10/2003, Post | 126.5 Titer |
| Age 18 to 59 Years | Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | A/New Caledonia/20/99 (H1N1), Pre | 51.8 Titer |
| Age 60 Years and Older | Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | B/Jiangsu/10/2003, Post | 104.8 Titer |
| Age 60 Years and Older | Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | A/New Caledonia/20/99 (H1N1), Pre | 34.8 Titer |
| Age 60 Years and Older | Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | A/New Caledonia/20/99 (H1N1), Post | 59.3 Titer |
| Age 60 Years and Older | Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | B/Jiangsu/10/2003, Pre | 42.6 Titer |
| Age 60 Years and Older | Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | A/New York/55/2004 (H3N2), Pre | 23.1 Titer |
| Age 60 Years and Older | Geometric Mean Titers (GMTs) of Hemagglutination Antibodies Before and After Fluzone® Vaccination | A/New York/55/2004 (H3N2), Post | 174.5 Titer |
Primary
Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination
Time frame: Day 0 to 3 post-vaccination
Population: Safety analysis was on all enrolled and vaccinated subjects intent-to-treat safety population with available reaction data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Solicited Injection Site Reaction | 40 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Erythema | 4 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Erythema (≥ 5.0 cm) | 1 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Pain (Unable to perform usual activities) | 0 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Solicited Systemic Reaction | 25 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Fever | 0 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Fever (≥ 102.3°F) | 0 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Headache | 12 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Swelling | 3 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Swelling (≥ 5.0 cm) | 1 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Pain | 39 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Headache (Prevents daily activity) | 1 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Malaise | 7 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Malaise (Prevents daily activity) | 0 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Myalgia | 13 Participants |
| Age 18 to 59 Years | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Myalgia (Prevents daily activity) | 0 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Myalgia (Prevents daily activity) | 0 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Solicited Injection Site Reaction | 10 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Headache (Prevents daily activity) | 0 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Erythema | 6 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Swelling | 3 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Erythema (≥ 5.0 cm) | 1 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Malaise (Prevents daily activity) | 0 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Pain (Unable to perform usual activities) | 0 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Swelling (≥ 5.0 cm) | 0 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Solicited Systemic Reaction | 9 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Malaise | 4 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Fever | 2 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Pain | 8 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Grade 3 Fever (≥ 102.3°F) | 0 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Myalgia | 3 Participants |
| Age 60 Years and Older | Number of Participants Reporting Solicited Injection Site and Solicited Systemic Reactions After Fluzone® Vaccination | Any Headache | 3 Participants |
Other Pre-specified
Percentage of Participants With ≥ 40 Serum Hemagglutination Inhibition Antibody Titers Post-vaccination.
Seroprotection: Percentage of participants with ≥ 40 serum hemagglutination inhibition antibody titers 21 days post-vaccination.
Time frame: 21 Days post-vaccination
Population: Seroprotection was assessed in the per-protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Age 18 to 59 Years | Percentage of Participants With ≥ 40 Serum Hemagglutination Inhibition Antibody Titers Post-vaccination. | A/New Caledonia/20/99 (H1N1) ≥ 40 | 90 Percentage of participants |
| Age 18 to 59 Years | Percentage of Participants With ≥ 40 Serum Hemagglutination Inhibition Antibody Titers Post-vaccination. | A/New York/55/2004 (H3N2) ≥ 40 | 95 Percentage of participants |
| Age 18 to 59 Years | Percentage of Participants With ≥ 40 Serum Hemagglutination Inhibition Antibody Titers Post-vaccination. | B/Jiangsu/10/2003 ≥ 40 | 86 Percentage of participants |
| Age 60 Years and Older | Percentage of Participants With ≥ 40 Serum Hemagglutination Inhibition Antibody Titers Post-vaccination. | B/Jiangsu/10/2003 ≥ 40 | 83 Percentage of participants |
| Age 60 Years and Older | Percentage of Participants With ≥ 40 Serum Hemagglutination Inhibition Antibody Titers Post-vaccination. | A/New Caledonia/20/99 (H1N1) ≥ 40 | 71 Percentage of participants |
| Age 60 Years and Older | Percentage of Participants With ≥ 40 Serum Hemagglutination Inhibition Antibody Titers Post-vaccination. | A/New York/55/2004 (H3N2) ≥ 40 | 83 Percentage of participants |
Other Pre-specified
Percentage of Participants With a ≥ 4-fold Increase in Serum Hemagglutination Inhibition Antibody Titers Post-vaccination
Seroconversion: percentage of participants with at least a 4-fold increase in serum hemagglutination inhibition antibody titers at 21 days post-vaccination.
Time frame: Day 21 post-vaccination
Population: Seroconversion was assessed in the per-protocol population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Age 18 to 59 Years | Percentage of Participants With a ≥ 4-fold Increase in Serum Hemagglutination Inhibition Antibody Titers Post-vaccination | A/New Caledonia/20/99 (H1N1) ≥ 4 fold-rise | 29 Percentage of participants |
| Age 18 to 59 Years | Percentage of Participants With a ≥ 4-fold Increase in Serum Hemagglutination Inhibition Antibody Titers Post-vaccination | A/New York/55/2004 (H3N2) ≥ 4 fold-rise | 93 Percentage of participants |
| Age 18 to 59 Years | Percentage of Participants With a ≥ 4-fold Increase in Serum Hemagglutination Inhibition Antibody Titers Post-vaccination | B/Jiangsu/10/2003 ≥ 4 fold-rise | 54 Percentage of participants |
| Age 60 Years and Older | Percentage of Participants With a ≥ 4-fold Increase in Serum Hemagglutination Inhibition Antibody Titers Post-vaccination | A/New Caledonia/20/99 (H1N1) ≥ 4 fold-rise | 9 Percentage of participants |
| Age 60 Years and Older | Percentage of Participants With a ≥ 4-fold Increase in Serum Hemagglutination Inhibition Antibody Titers Post-vaccination | A/New York/55/2004 (H3N2) ≥ 4 fold-rise | 67 Percentage of participants |
| Age 60 Years and Older | Percentage of Participants With a ≥ 4-fold Increase in Serum Hemagglutination Inhibition Antibody Titers Post-vaccination | B/Jiangsu/10/2003 ≥ 4 fold-rise | 27 Percentage of participants |