Influenza, Human
Conditions
Brief summary
A Phase 3, randomized, observer-blinded, active-controlled trial to evaluate the immunogenicity and safety of a recombinant quadrivalent nanoparticle influenza vaccine with Matrix-M1 adjuvant (NanoFlu) compared with a licensed quadrivalent inactivated influenza vaccine in adults ≥ 65 years of age. Both vaccines were formulated with the 4 influenza strains recommended for the 2019-20 Northern hemisphere influenza season. 2654 subjects were enrolled and randomized into 1 of 2 treatment groups to receive either NanoFlu or active comparator. Subjects were followed for approximately 1 year following injection; with primary immunogenicity analyses based on Day 28 sera. This trial was conducted in the United States at approximately 19 clinical sites.
Interventions
BIOLOGICALNanoFlu
Investigational quadrivalent seasonal influenza vaccine for the 2019-20 Northern hemisphere influenza season.
BIOLOGICALFluzone Quadrivalent
Licensed quadrivalent seasonal influenza vaccine for the 2019-20 Northern hemisphere influenza season.
Sponsors
Novavax
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
1. Clinically-stable adult male or female, ≥ 65 years of age. Subjects may have 1 or more chronic medical diagnoses, but should be clinically stable as assessed by: * Ambulatory status, living independently in the community or in a residential facility providing minimal assistance (eg, meal preparation and transport), * Absence of changes in medical therapy within 1 month due to treatment failure or toxicity, * Absence of medical events qualifying as serious adverse events within the prior 2 months, and * Absence of known, current, and life-limiting diagnoses which render survival to completion of the protocol unlikely in the opinion of the investigator. 2. Willing and able to give informed consent prior to trial enrollment, and 3. Living in the community and able to attend trial visits, comply with trial requirements, and provide timely, reliable, and complete reports of adverse events.
Exclusion criteria
1. Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of study vaccination. 2. Participation in any previous Novavax influenza vaccine clinical trial(s). 3. History of a serious reaction to prior influenza vaccination, known allergy to constituents of Fluzone Quadrivalent or polysorbate 80. 4. History of Guillain-Barré Syndrome (GBS) within 6 weeks following a previous influenza vaccine. 5. Received any vaccine in the 4 weeks preceding the trial vaccination and any influenza vaccine within 6 months preceding the trial vaccination. 6. Any known or suspected immunosuppressive illness, congenital or acquired, based on medical history and/or physical examination. 7. Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the trial vaccine. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted. 8. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the trial vaccine. 9. Acute disease at the time of enrollment (defined as the presence of a moderate or severe illness with or without fever, or an oral temperature ≥ 38.0°C, on the planned day of vaccine administration). 10. Any condition that in the opinion of the investigator would pose a health risk to the subject if enrolled or could interfere with evaluation of the vaccine or interpretation of trial results (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting). 11. Known disturbance of coagulation. 12. Suspicion or recent history (within 1 year of planned vaccination) of alcohol or other substance abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With MAAEs, SAEs, SNMCs | Day 0 - Day 27 | Number of subjects with MAEs, SAEs, and SNMCs - including AESIs. |
| HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR) | Day 28 | Egg-Based HAI Assay responses for all 4 vaccine homologous influenza strains (ie, 2 influenza A and 2 influenza B strains) expressed as GMFR on Day 28 |
| Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants | Day 0 - Day 28 | Egg-Based HAI Assay responses for all 4 vaccine homologous influenza strains (ie, 2 influenza A and 2 influenza B strains) summarized in terms of SCR on Day 28 |
| Number of Subjects With Solicited Local and Systemic Adverse Events (AEs) | Day 0 - Day 6 | Number of subjects with solicited local and systemic AEs over 7 days post-injection (ie, Day 0 through Day 6, inclusive). |
| Number of Subjects With Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs) | Day 0 - Day 364 | Number of subjects with Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs) - including AESIs - through 1-year post-injection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28 - 364 | Wild-Type HAI Assay Homologous influenza strains and 1 antigenically drifted strain expressed as GMFR. |
| Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28 - Day 364 | Wild-Type HAI Assay Homologous Influenza Strains and at least 1 Antigenically Drifted Strain Expressed as Seroconversion Rate (SCR). |
| Subjects Who Seroprotected as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as SPR | Day 28 | Homologous Influenza Strains and at least 1 Antigenically Drifted Strain Expressed as Seroprotection Rate (SPR). |
| HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 0 - Day 28 | Homologous influenza strains and 1 antigenically drifted strain expressed as GMT |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NanoFlu NanoFlu will be administered as a single dose (0.5 mL) in the arm muscle on Day 0.
NanoFlu: Investigational quadrivalent seasonal influenza vaccine for the 2019-20 Northern hemisphere influenza season. | 1,333 |
| Fluzone Quadrivalent Fluzone Quadrivalent will be administered as a single dose (0.5 mL) in the arm muscle on Day 0.
Fluzone Quadrivalent: Licensed quadrivalent seasonal influenza vaccine for the 2019-20 Northern hemisphere influenza season. | 1,319 |
| Total | 2,652 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 |
| Overall Study | Lost to Follow-up | 11 | 8 |
| Overall Study | Miscellaneous | 4 | 5 |
| Overall Study | Voluntary withdrawal unrelated to adverse event | 1 | 2 |
Baseline characteristics
| Characteristic | Fluzone Quadrivalent | Total | NanoFlu |
|---|---|---|---|
| Age, Continuous | 72.5 years STANDARD_DEVIATION 5.7 | 72.5 years STANDARD_DEVIATION 5.7 | 72.5 years STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 65 Participants | 129 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1254 Participants | 2523 Participants | 1269 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 17 Participants | 14 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 17 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 103 Participants | 208 Participants | 105 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1200 Participants | 2408 Participants | 1208 Participants |
| Reaction from vaccine within the past 3 years | 3 Participants | 6 Participants | 3 Participants |
| Received 2018-2019 Influenza Vaccine | 1102 Participants | 2219 Participants | 1117 Participants |
| Received any influenza vaccination within the past 3 years | 1200 Participants | 2410 Participants | 1210 Participants |
| Sex: Female, Male Female | 845 Participants | 1637 Participants | 792 Participants |
| Sex: Female, Male Male | 474 Participants | 1015 Participants | 541 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 1,333 | 8 / 1,319 |
| other Total, other adverse events | 0 / 1,333 | 0 / 1,319 |
| serious Total, serious adverse events | 136 / 1,333 | 125 / 1,319 |
Outcome results
Primary
HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR)
Egg-Based HAI Assay responses for all 4 vaccine homologous influenza strains (ie, 2 influenza A and 2 influenza B strains) expressed as GMFR on Day 28
Time frame: Day 28
Population: Per-Protocol (PP) Population including all subjects who provided consent, were randomized and received the assigned dose of the test article according to protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| NanoFlu | HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR) | A/Brisbane/02/2018 (H1N1) | 1.9 Geometric Mean Fold Ratio |
| NanoFlu | HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR) | B/Maryland/15/2016 (Victoria lineage) | 1.6 Geometric Mean Fold Ratio |
| NanoFlu | HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR) | A/Kansas/14/2017 (H3N2) | 2.7 Geometric Mean Fold Ratio |
| NanoFlu | HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR) | B/Phuket/3073/2013 (Yamagata lineage) | 2.4 Geometric Mean Fold Ratio |
| Fluzone Quadrivalent | HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR) | B/Phuket/3073/2013 (Yamagata lineage) | 2.0 Geometric Mean Fold Ratio |
| Fluzone Quadrivalent | HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR) | A/Brisbane/02/2018 (H1N1) | 1.7 Geometric Mean Fold Ratio |
| Fluzone Quadrivalent | HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR) | A/Kansas/14/2017 (H3N2) | 2.3 Geometric Mean Fold Ratio |
| Fluzone Quadrivalent | HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as Ratio of Geometric Mean Fold Ratio (GMFR) | B/Maryland/15/2016 (Victoria lineage) | 1.5 Geometric Mean Fold Ratio |
Primary
Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants
Egg-Based HAI Assay responses for all 4 vaccine homologous influenza strains (ie, 2 influenza A and 2 influenza B strains) summarized in terms of SCR on Day 28
Time frame: Day 0 - Day 28
Population: Per-Protocol (PP) Population including all subjects who provided consent, were randomized and received the assigned dose of the test article according to protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NanoFlu | Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants | A/Brisbane/02/2018 (H1N1) pdm09 | 22.0 percentage of participants |
| NanoFlu | Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants | A/Kansas/14/2017 (H3N2) | 41.8 percentage of participants |
| NanoFlu | Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants | B/Maryland/15/2016 (Victoria lineage) | 11.2 percentage of participants |
| NanoFlu | Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants | B/Phuket/3073/2013 (Yamagata lineage) | 31.3 percentage of participants |
| Fluzone Quadrivalent | Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants | B/Phuket/3073/2013 (Yamagata lineage) | 22.9 percentage of participants |
| Fluzone Quadrivalent | Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants | A/Brisbane/02/2018 (H1N1) pdm09 | 17.0 percentage of participants |
| Fluzone Quadrivalent | Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants | B/Maryland/15/2016 (Victoria lineage) | 10.7 percentage of participants |
| Fluzone Quadrivalent | Mean Difference in the Seroconversion Rate (SCR) HAI Antibody Responses for Vaccine Homologous Influenza Strains Expressed as a Percentage of Participants | A/Kansas/14/2017 (H3N2) | 34.4 percentage of participants |
Primary
Number of Subjects With MAAEs, SAEs, SNMCs
Number of subjects with MAEs, SAEs, and SNMCs - including AESIs.
Time frame: Day 0 - Day 27
Population: Safety Population, including all study subjects who provided consent, were randomized and received a test article. The Safety Population was analyzed as actually treated (ie, based on the actual dose received).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NanoFlu | Number of Subjects With MAAEs, SAEs, SNMCs | MAAEs | 108 participants |
| NanoFlu | Number of Subjects With MAAEs, SAEs, SNMCs | SAEs | 10 participants |
| NanoFlu | Number of Subjects With MAAEs, SAEs, SNMCs | SNMCs | 4 participants |
| Fluzone Quadrivalent | Number of Subjects With MAAEs, SAEs, SNMCs | SAEs | 5 participants |
| Fluzone Quadrivalent | Number of Subjects With MAAEs, SAEs, SNMCs | SNMCs | 11 participants |
| Fluzone Quadrivalent | Number of Subjects With MAAEs, SAEs, SNMCs | MAAEs | 108 participants |
Primary
Number of Subjects With Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs)
Number of subjects with Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs) - including AESIs - through 1-year post-injection.
Time frame: Day 0 - Day 364
Population: Safety Population, including all study subjects who provided consent, were randomized, and received a test article. The Safety Population was analyzed as actually treated (ie, based on the actual dose received).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NanoFlu | Number of Subjects With Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs) | SAEs | 81 participants |
| NanoFlu | Number of Subjects With Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs) | SNMCs | 42 participants |
| NanoFlu | Number of Subjects With Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs) | MAAEs | 353 participants |
| Fluzone Quadrivalent | Number of Subjects With Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs) | SAEs | 78 participants |
| Fluzone Quadrivalent | Number of Subjects With Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs) | SNMCs | 49 participants |
| Fluzone Quadrivalent | Number of Subjects With Medically Attended Adverse Events (MAAEs), Serious Adverse Events (SAEs), Significant New Medical Conditions (SNMCs) | MAAEs | 354 participants |
Primary
Number of Subjects With Solicited Local and Systemic Adverse Events (AEs)
Number of subjects with solicited local and systemic AEs over 7 days post-injection (ie, Day 0 through Day 6, inclusive).
Time frame: Day 0 - Day 6
Population: Safety Population, including all study subjects who provided consent, were randomized, and received a test article. The Safety Population was analyzed as actually treated (ie, based on the actual dose received).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NanoFlu | Number of Subjects With Solicited Local and Systemic Adverse Events (AEs) | Local solicited TEAEs | 372 participants |
| NanoFlu | Number of Subjects With Solicited Local and Systemic Adverse Events (AEs) | Systemic Solicited TEAEs | 369 participants |
| Fluzone Quadrivalent | Number of Subjects With Solicited Local and Systemic Adverse Events (AEs) | Local solicited TEAEs | 243 participants |
| Fluzone Quadrivalent | Number of Subjects With Solicited Local and Systemic Adverse Events (AEs) | Systemic Solicited TEAEs | 292 participants |
Secondary
HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR)
Wild-Type HAI Assay Homologous influenza strains and 1 antigenically drifted strain expressed as GMFR.
Time frame: Day 28 - 364
Population: Per-Protocol (PP) Population including all subjects who provided consent, were randomized and received the assigned dose of the test article according to protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28 - A/Kansas (H3N2) | 5.6 Geometric Mean Fold Rise |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 364- A/Brisbane (H1N1) | 2.0 Geometric Mean Fold Rise |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28 - B/Phuket (Yamagata Linage) | 2.6 Geometric Mean Fold Rise |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 364 - A/Kansas (H3N2) | 2.9 Geometric Mean Fold Rise |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28- A/Brisbane (H1N1) | 2.4 Geometric Mean Fold Rise |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 364 - B/ Maryland (Victoria Lineage) | 2.0 Geometric Mean Fold Rise |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28 - A/California (H3N2) | 2.6 Geometric Mean Fold Rise |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 364 - B/Phuket (Yamagata Linage) | 1.1 Geometric Mean Fold Rise |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28 - B/ Maryland (Victoria Lineage) | 2.1 Geometric Mean Fold Rise |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 364 - A/California (H3N2) | 79.6 Geometric Mean Fold Rise |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28 - A/Cardiff (H3N2) | 2.4 Geometric Mean Fold Rise |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 364 - A/Cardiff (H3N2) | 2.0 Geometric Mean Fold Rise |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28 - A/Cardiff (H3N2) | 1.8 Geometric Mean Fold Rise |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28- A/Brisbane (H1N1) | 1.9 Geometric Mean Fold Rise |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28 - A/Kansas (H3N2) | 3.4 Geometric Mean Fold Rise |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28 - B/ Maryland (Victoria Lineage) | 1.6 Geometric Mean Fold Rise |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28 - B/Phuket (Yamagata Linage) | 1.8 Geometric Mean Fold Rise |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 28 - A/California (H3N2) | 1.8 Geometric Mean Fold Rise |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 364 - A/Cardiff (H3N2) | 1.5 Geometric Mean Fold Rise |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 364- A/Brisbane (H1N1) | 2.0 Geometric Mean Fold Rise |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 364 - A/Kansas (H3N2) | 2.2 Geometric Mean Fold Rise |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 364 - B/ Maryland (Victoria Lineage) | 1.8 Geometric Mean Fold Rise |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 364 - B/Phuket (Yamagata Linage) | 1.1 Geometric Mean Fold Rise |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Fold Ratio (GMFR) | Day 364 - A/California (H3N2) | 75.7 Geometric Mean Fold Rise |
Secondary
HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT)
Homologous influenza strains and 1 antigenically drifted strain expressed as GMT
Time frame: Day 0 - Day 28
Population: Per-Protocol (PP) Population including all subjects provided consent, were randomized and received the assigned dose of the test article according to protocol, had HAI serology results for Day 0 and Day 28, and had no major protocol deviations affecting the primary immunogenicity outcomes as determined by the sponsor prior to database lock and unblinding.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 0 - A/ Brisbane (H1N1) | 26.2 titers |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 28 - A / Brisbane (H1N1) | 49.3 titers |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 0 - A/ Kansas (H3N2) | 55.1 titers |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 28- A/ Kansas (H3N2) | 151.5 titers |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 0 - B (Victoria Lineage) | 70.7 titers |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 28 - B (Victoria Lineage) | 110.7 titers |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 0 - B (Yamagata Lineage) | 69.1 titers |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 28- B (Yamagata Lineage) | 168.5 titers |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 0 - A/California (H3N2) | 44.5 titers |
| NanoFlu | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 28- A/California (H3N2) | 115.0 titers |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 28- B (Yamagata Lineage) | 133.9 titers |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 0 - A/ Brisbane (H1N1) | 26.0 titers |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 28 - B (Victoria Lineage) | 106.3 titers |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 28 - A / Brisbane (H1N1) | 45.0 titers |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 28- A/California (H3N2) | 80.6 titers |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 0 - A/ Kansas (H3N2) | 54.7 titers |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 0 - B (Yamagata Lineage) | 66.5 titers |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 28- A/ Kansas (H3N2) | 126.8 titers |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 0 - A/California (H3N2) | 44.0 titers |
| Fluzone Quadrivalent | HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as Geometric Mean Titers (GMT) | Day 0 - B (Victoria Lineage) | 69.8 titers |
Secondary
Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain
Wild-Type HAI Assay Homologous Influenza Strains and at least 1 Antigenically Drifted Strain Expressed as Seroconversion Rate (SCR).
Time frame: Day 28 - Day 364
Population: Per-Protocol (PP) Population including all subjects who provided consent, were randomized and received the assigned dose of the test article according to protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NanoFlu | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 364 - A/California (H3N2) | 19.0 percentage of participants |
| NanoFlu | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28- B/Phuket/3073/2013 (Yamagata lineage) | 35.4 percentage of participants |
| NanoFlu | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 364 - A/Cardiff (H3N2) | 22.2 percentage of participants |
| NanoFlu | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28-A/Kansas/14/2017 (H3N2) | 69.8 percentage of participants |
| NanoFlu | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 364- A/Brisbane/02/2018 (H1N1) pdm09 | 19.0 percentage of participants |
| NanoFlu | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28 - A/California (H3N2) | 37.1 percentage of participants |
| NanoFlu | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 364-A/Kansas/14/2017 (H3N2) | 54.0 percentage of participants |
| NanoFlu | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28- A/Brisbane/02/2018 (H1N1) pdm09 | 32.7 percentage of participants |
| NanoFlu | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 364- B/Maryland/15/2016 (Victoria lineage) | 17.5 percentage of participants |
| NanoFlu | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28 - A/Cardiff (H3N2) | 32.7 percentage of participants |
| NanoFlu | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 364- B/Phuket/3073/2013 (Yamagata lineage) | 6.3 percentage of participants |
| NanoFlu | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28- B/Maryland/15/2016 (Victoria lineage) | 25.1 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 364- B/Phuket/3073/2013 (Yamagata lineage) | 3.6 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28- A/Brisbane/02/2018 (H1N1) pdm09 | 21.4 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28-A/Kansas/14/2017 (H3N2) | 49.5 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28- B/Phuket/3073/2013 (Yamagata lineage) | 17.7 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28 - A/California (H3N2) | 20.5 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28 - A/Cardiff (H3N2) | 18.6 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 364 - A/California (H3N2) | 5.4 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 364 - A/Cardiff (H3N2) | 7.1 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 364- A/Brisbane/02/2018 (H1N1) pdm09 | 19.6 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 364-A/Kansas/14/2017 (H3N2) | 28.6 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 364- B/Maryland/15/2016 (Victoria lineage) | 8.9 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroconverted as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain | Day 28- B/Maryland/15/2016 (Victoria lineage) | 13.5 percentage of participants |
Secondary
Subjects Who Seroprotected as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as SPR
Homologous Influenza Strains and at least 1 Antigenically Drifted Strain Expressed as Seroprotection Rate (SPR).
Time frame: Day 28
Population: Per-Protocol (PP) Population including all subjects provided consent, were randomized and received the assigned dose of the test article according to protocol, had HAI serology results for Day 0 and Day 28, and had no major protocol deviations affecting the primary immunogenicity outcomes as determined by the sponsor prior to database lock and unblinding.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NanoFlu | Subjects Who Seroprotected as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as SPR | A/Brisbane/02/2018 (H1N1) pdm09 | 69.1 percentage of participants |
| NanoFlu | Subjects Who Seroprotected as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as SPR | A/Kansas/14/2017 (H3N2) | 98.8 percentage of participants |
| NanoFlu | Subjects Who Seroprotected as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as SPR | B/Maryland/15/2016 (Victoria lineage) | 99.1 percentage of participants |
| NanoFlu | Subjects Who Seroprotected as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as SPR | B/Phuket/3073/2013 (Yamagata lineage) | 99.0 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroprotected as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as SPR | B/Phuket/3073/2013 (Yamagata lineage) | 97.5 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroprotected as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as SPR | A/Brisbane/02/2018 (H1N1) pdm09 | 64.5 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroprotected as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as SPR | B/Maryland/15/2016 (Victoria lineage) | 98.7 percentage of participants |
| Fluzone Quadrivalent | Subjects Who Seroprotected as Determined by HAI Titers to All Vaccine Homologous Influenza Strains and at Least 1 Antigenically Drifted Strain Expressed as SPR | A/Kansas/14/2017 (H3N2) | 98.3 percentage of participants |