Influenza
Conditions
Keywords
Influenza, Influenza virus vaccine, Fluzone® Quadrivalent Influenza Vaccine (No Preservative)
Brief summary
The aim of the study was to describe the safety and immunogenicity of a 0.5-mL dose (15 μg hemagglutinin \[HA\] per strain) of Fluzone Quadrivalent vaccine in children 6 to \<36 months of age. Primary objective: * To compare the rate of any fever (temperature ≥100.4 degrees Fahrenheit \[38.0 degrees Celsius) following a 0.5-mL dose of Fluzone Quadrivalent vaccine to that following a 0.25-mL dose of Fluzone Quadrivalent vaccine during the 7 days after either vaccination (Dose 1 and Dose 2 combined) in participants 6 to \< 36 months of age. Secondary objective: * To compare antibody responses induced by a 0.5-mL dose of Fluzone Quadrivalent vaccine to those induced by a 0.25-mL dose of Fluzone Quadrivalent vaccine as assessed by geometric mean titer (GMT) ratios and seroconversion rate differences after the final vaccination in participants 6 to \< 36 months of age. Other objectives: * To describe the safety of 2 different dose levels of the 2016-2017 formulation of Fluzone Quadrivalent vaccine in participants 6 to \< 36 months of age. * To describe the immunogenicity of 2 different dose levels of the 2016-2017 formulation of Fluzone Quadrivalent vaccine in participants 6 months to \< 36 months of age. * To submit available sera from approximately 30 participants to the Center for Biologics Evaluation and Research for further analysis by the World Health Organization, the Centers for Disease Control and Prevention, and the FDA to support formulation recommendations for subsequent influenza vaccines.
Detailed description
All participants received 1 intramuscular dose of Fluzone Quadrivalent vaccine during Visit 1. For participants, for whom 2 doses of influenza vaccine were recommended per Advisory Committee on Immunization Practices (ACIP) guidance, a second dose of Fluzone Quadrivalent vaccine (of the same volume as the first dose) was administered during Visit 2 (28 days after Visit 1). Solicited adverse event (AE) information was collected for 7 days after each vaccination, unsolicited AE information was collected from Visit 1 to Visit 2 or to Visit 3 for participants receiving 2 doses of study vaccine. Serious adverse event (SAE) information was collected for 28 days after each vaccination. Immunogenicity was evaluated in a planned subset of 1600 randomly selected participants prior to vaccination on Day 0 (Visit 1) and at Day 28 after the final vaccination.
Interventions
BIOLOGICALFluzone Quadrivalent vaccine, No Preservative
0.25-mL (Pediatric Dose), Intramuscular (2016-2017 formulation)
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to 35 Months
Healthy volunteers
Yes
Inclusion criteria
* Aged 6 to \< 36 months of age on the day of first study vaccination (study product administration). * Born at full term of pregnancy (≥37 weeks) and/or with a birth weight ≥2.5 kg. Note: This inclusion criterion only applies to participants 6 to \<12 months of age on the day of the first study visit. * Informed consent form has been signed and dated by the parent(s) or guardian(s). * Participant and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures.
Exclusion criteria
* Participation at the time of study enrollment (or in the 30 days preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure. * Receipt of any vaccine in the 30 days preceding the first trial vaccination, or planned receipt of any vaccine before Visit 2 for participants receiving 1 dose of influenza vaccine or Visit 3 for participants receiving 2 doses of influenza vaccine. * Previous vaccination against influenza (in the 2016-2017 season) with either the trial vaccine or another vaccine. * Receipt of immune globulins, blood, or blood-derived products in the past 3 months. * 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). * Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances. * Thrombocytopenia, which may be a contraindication for intramuscular vaccination, at the discretion of the Investigator. * Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination. * Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily. * Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion. * Moderate or severe acute illness/infection (according to Investigator judgment) on the day of planned vaccination or febrile illness (temperature ≥100.4 degrees Fahrenheit \[38.0 degrees Celsius\]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided. * Identified as a natural or adopted child of either the Investigator or an employee with direct involvement in the proposed study. * History of serious adverse reactions to any influenza vaccine. * Personal history of Guillain-Barré syndrome. * Any condition that in the opinion of the Investigator would pose a health risk to the participant if enrolled or could interfere with the evaluation of the vaccine. * Personal history of clinically significant developmental delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder. * Known seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Fever (Fever Rate) Following Vaccination With Fluzone Quadrivalent Vaccine | Within 7 days after any vaccination | Fever rate was defined as percentage of participants with fever (temperature \>=100.4 degrees Fahrenheit \[38.0 degrees Celsius\]) following vaccination with Fluzone Quadrivalent vaccine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies | 28 days post-final vaccination | Anti-influenza antibodies were measured using a hemagglutination inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. |
| Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens | 28 days post-final vaccination | Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. SCR was defined as percentage of participants with either a pre-vaccination titer \<10 (1/dil) and a post-final vaccination titer \>=40 (1/dil), or a pre-vaccination titer \>=10 (1/dil) and at least a four-fold increase in post-final vaccination titer. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
Study participants were enrolled in 38 centers in the United States from 23 September 2016 to 02 January 2017.
Pre-assignment details
A total of 1950 participants were randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Fluzone Quadrivalent Vaccine, 0.25-mL Participants received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.25-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28. | 949 |
| Fluzone Quadrivalent Vaccine, 0.5-mL Participants received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second 0.5-mL dose of Fluzone Quadrivalent vaccine was administered at Day 28. | 992 |
| Total | 1,941 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Lost to Follow-up | 19 | 22 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Protocol Violation | 20 | 27 |
| Overall Study | Withdrawal by Subject | 22 | 29 |
Baseline characteristics
| Characteristic | Fluzone Quadrivalent Vaccine, 0.5-mL | Fluzone Quadrivalent Vaccine, 0.25-mL | Total |
|---|---|---|---|
| Age, Continuous | 20.5 Months STANDARD_DEVIATION 8.55 | 20.4 Months STANDARD_DEVIATION 8.75 | 20.5 Months STANDARD_DEVIATION 8.65 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 221 Participants | 206 Participants | 427 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 763 Participants | 731 Participants | 1494 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 12 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 10 Participants | 9 Participants | 19 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 195 Participants | 178 Participants | 373 Participants |
| Race (NIH/OMB) More than one race | 43 Participants | 36 Participants | 79 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) White | 725 Participants | 717 Participants | 1442 Participants |
| Region of Enrollment United States | 992 participants | 949 participants | 1941 participants |
| Sex: Female, Male Female | 495 Participants | 469 Participants | 964 Participants |
| Sex: Female, Male Male | 497 Participants | 480 Participants | 977 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 949 | 0 / 992 |
| other Total, other adverse events | 698 / 949 | 737 / 992 |
| serious Total, serious adverse events | 5 / 949 | 5 / 992 |
Outcome results
Primary
Percentage of Participants With Fever (Fever Rate) Following Vaccination With Fluzone Quadrivalent Vaccine
Fever rate was defined as percentage of participants with fever (temperature \>=100.4 degrees Fahrenheit \[38.0 degrees Celsius\]) following vaccination with Fluzone Quadrivalent vaccine.
Time frame: Within 7 days after any vaccination
Population: Analysis was performed using the safety analysis set. Here, 'Number of participants analyzed' = those participants with available data for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluzone Quadrivalent Vaccine, 0.25-mL | Percentage of Participants With Fever (Fever Rate) Following Vaccination With Fluzone Quadrivalent Vaccine | 11.31 percentage of participants |
| Fluzone Quadrivalent Vaccine, 0.5-mL | Percentage of Participants With Fever (Fever Rate) Following Vaccination With Fluzone Quadrivalent Vaccine | 12.15 percentage of participants |
Comparison: Difference in fever rate was defined as the fever rate following a 0.5-mL dose of Fluzone Quadrivalent vaccine minus the fever rate following a 0.25-mL dose of Fluzone Quadrivalent vaccine.95% CI: [-2.13, 3.8]
Secondary
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies
Anti-influenza antibodies were measured using a hemagglutination inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage.
Time frame: 28 days post-final vaccination
Population: Analysis was performed using Per-protocol (PP) analysis set which included participants who received at least 1 dose of study vaccine and had a valid post-vaccination serologic result for at least 1 strain without any protocol deviations. Here, 'Number Analyzed' = those participants with available data for specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Fluzone Quadrivalent Vaccine, 0.25-mL | Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies | A/H1N1 | 214 Titers (1/dilutions [dil]) |
| Fluzone Quadrivalent Vaccine, 0.25-mL | Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies | A/H3N2 | 221 Titers (1/dilutions [dil]) |
| Fluzone Quadrivalent Vaccine, 0.25-mL | Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies | B Victoria | 261 Titers (1/dilutions [dil]) |
| Fluzone Quadrivalent Vaccine, 0.25-mL | Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies | B Yamagata | 243 Titers (1/dilutions [dil]) |
| Fluzone Quadrivalent Vaccine, 0.5-mL | Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies | B Yamagata | 349 Titers (1/dilutions [dil]) |
| Fluzone Quadrivalent Vaccine, 0.5-mL | Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies | A/H1N1 | 310 Titers (1/dilutions [dil]) |
| Fluzone Quadrivalent Vaccine, 0.5-mL | Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies | B Victoria | 348 Titers (1/dilutions [dil]) |
| Fluzone Quadrivalent Vaccine, 0.5-mL | Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies | A/H3N2 | 332 Titers (1/dilutions [dil]) |
Comparison: For A/H1N1 strain, GMT ratio was defined as the GMT after 0.5 mL dose(s) of Fluzone Quadrivalent vaccine divided by the GMT after 0.25 mL dose(s) of Fluzone Quadrivalent vaccine.95% CI: [1.19, 1.77]
Comparison: For A/H3N2 strain, GMT ratio was defined as the GMT after 0.5 mL dose(s) of Fluzone Quadrivalent vaccine divided by the GMT after 0.25 mL dose(s) of Fluzone Quadrivalent vaccine.95% CI: [1.23, 1.83]
Comparison: For B Victoria lineage strain, GMT ratio was defined as the GMT after 0.5 mL dose(s) of Fluzone Quadrivalent vaccine divided by the GMT after 0.25 mL dose(s) of Fluzone Quadrivalent vaccine.95% CI: [1.1, 1.62]
Comparison: For B Yamagata lineage strain, GMT ratio was defined as the GMT after 0.5 mL dose(s) of Fluzone Quadrivalent vaccine divided by the GMT after 0.25 mL dose(s) of Fluzone Quadrivalent vaccine.95% CI: [1.2, 1.73]
Secondary
Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens
Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. SCR was defined as percentage of participants with either a pre-vaccination titer \<10 (1/dil) and a post-final vaccination titer \>=40 (1/dil), or a pre-vaccination titer \>=10 (1/dil) and at least a four-fold increase in post-final vaccination titer.
Time frame: 28 days post-final vaccination
Population: Analysis was performed using the PP analysis set. Here, 'Number Analyzed' = those participants with available data for specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluzone Quadrivalent Vaccine, 0.25-mL | Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens | A/H1N1 | 78.9 percentage of participants |
| Fluzone Quadrivalent Vaccine, 0.25-mL | Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens | A/H3N2 | 81.9 percentage of participants |
| Fluzone Quadrivalent Vaccine, 0.25-mL | Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens | B Victoria | 87.2 percentage of participants |
| Fluzone Quadrivalent Vaccine, 0.25-mL | Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens | B Yamagata | 87.8 percentage of participants |
| Fluzone Quadrivalent Vaccine, 0.5-mL | Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens | B Yamagata | 91.2 percentage of participants |
| Fluzone Quadrivalent Vaccine, 0.5-mL | Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens | A/H1N1 | 84.1 percentage of participants |
| Fluzone Quadrivalent Vaccine, 0.5-mL | Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens | B Victoria | 88.6 percentage of participants |
| Fluzone Quadrivalent Vaccine, 0.5-mL | Percentage of Participants With Seroconversion (Seroconversion Rate [SCR]) to Influenza Vaccine Antigens | A/H3N2 | 86.2 percentage of participants |
Comparison: For A/H1N1 strain, difference in SCR was defined as SCR after 0.5-mL dose(s) of Fluzone Quadrivalent Vaccine minus SCR after 0.25-mL dose(s) of Fluzone Quadrivalent Vaccine.95% CI: [0.189, 10]
Comparison: For A/H3N2 strain, difference in SCR was defined as SCR after 0.5-mL dose(s) of Fluzone Quadrivalent Vaccine minus SCR after 0.25-mL dose(s) of Fluzone Quadrivalent Vaccine.95% CI: [-0.283, 8.99]
Comparison: For B Victoria lineage strain, difference in SCR was defined as SCR after 0.5-mL dose(s) of Fluzone Quadrivalent Vaccine minus SCR after 0.25-mL dose(s) of Fluzone Quadrivalent Vaccine.95% CI: [-2.78, 5.56]
Comparison: For B Yamagata lineage strain, difference in SCR was defined as SCR after 0.5-mL dose(s) of Fluzone Quadrivalent Vaccine minus SCR after 0.25-mL dose(s) of Fluzone Quadrivalent Vaccine.95% CI: [-0.465, 7.36]