Influenza, Human
Conditions
Keywords
influenza, vaccine, MF59, adjuvant
Brief summary
This Phase 2, randomized, observer-blind, dose-confirmation clinical study evaluated different formulations of MF59-Adjuvanted Quadrivalent Subunit Inactivated Influenza Vaccine. Approximately 1000 subjects were randomized into 1 of 4 possible treatment groups with approximately 250 participants per group. Every participant received an influenza vaccine injection on Day 1 and were to be followed up for approximately 6 months following injection. The primary immunogenicity analysis is based on Day 29 serology data.
Interventions
BIOLOGICALExperimental: IIV-A Investigational IIV-A administered as a single dose intramuscularly on Day 1
Biological/Vaccine: Investigational IIV-A Investigational Quadrivalent Influenza vaccine (higher hemagglutinin \[HA\] dose), containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO (World Health Organization) for quadrivalent vaccines for the respective season.
BIOLOGICALExperimental: aIIV-B Investigational aIIV-B administered as a single dose intramuscularly on Day 1
Biological/Vaccine: Investigational aIIV-B Investigational MF59 Adjuvanted Quadrivalent Influenza vaccine (higher HA dose, standard dose MF59), containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO (World Health Organization) for quadrivalent vaccines for the respective season.
BIOLOGICALExperimental: aIIV-C Investigational aIIV-C administered as a single dose intramuscularly on Day 1
Biological/Vaccine: Investigational aIIV-C Investigational MF59 Adjuvanted Quadrivalent Influenza vaccine (higher HA dose, higher dose MF59), containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO (World Health Organization) for quadrivalent vaccines for the respective season.
BIOLOGICALActive Comparator: Licensed IIV IIV administered as a single dose intramuscularly on Day 1
Biological/Vaccine: Licensed IIV Licensed Non-adjuvanted Quadrivalent Influenza vaccine (standard HA dose), containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO (World Health Organization) for quadrivalent vaccines for the respective season.
Sponsors
Seqirus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
In order to participate in this study, all subjects must meet ALL of the inclusion criteria described. 1. Individuals ≥50 years of age on the day of informed consent. 2. Individuals who have voluntarily given written consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. 3. Individuals who can comply with study procedures including follow-up . 4. Males, females of non-childbearing potential or females of childbearing potential who are using an effective birth control method, at least 30 days prior to informed consent, which they intend to use for at least 2 months after the study vaccination. \-
Exclusion criteria
In order to participate in this study, all subjects must not meet ANY of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity Endpoint: Geometric Mean Titer (GMT): Geometric Mean of Hemagglutination Inhibition (HI) Antibodies at Day 1 and Day 29 | Day 1 and Day 29 | GMTs on Day 1 (prior to vaccination) and Day 29 as determined by HI assay against each of the 4 vaccine strains. No hypothesis testing was performed for the primary immunogenicity objectives. |
| Immunogenicity Endpoint: Geometric Mean Fold Increase (GMFI) (HI Assay) | Day 1 to Day 29 | Geometric mean of the fold increase in serum HI titer postvaccination (Day 29) compared to prevaccination (Day 1) for each of the 4 vaccine strains. |
| Immunogenicity Endpoint: Percentages of Subjects With HI Titers ≥1:40 at Day 1 and Day 29 | Day 1 and Day 29 | Percentages of subjects with HI titers ≥1:40 at Day 1 and Day 29 for each of the 4 vaccine strains. |
| Immunogenicity Endpoint: Percentage of Subjects With Seroconversion at Day 29 (HI Assay) | Day 1 to Day 29 | Seroconversion is defined as ≥4-fold increase in titer postvaccination in those with prevaccination titer equal to or above the lower limit of quantitation (LLOQ; 1:10), or a postvaccination titer ≥1:40 for subjects with baseline titer below the LLOQ (1:10) for HI antibodies. |
| Immunogenicity Endpoint: GMT Ratio (HI Assay) | Day 29 | The GMT ratio is the geometric mean of the postvaccination HI titer for the investigational vaccine over the geometric mean of the postvaccination HI titer for the licensed IIV vaccine. The Day 29 GMT ratios are calculated for the investigational vaccines with reference to the licensed vaccine, ie, the Day 29 GMT ratios are the ratio of the Day 29 GMTs in the Investigational group (IIV-A Investigational, aIIV-B Investigational, or aIIV-C Investigational) compared with the Day 29 GMTs in the Licensed IIV group (ie, Investigational group/Licensed IIV group). As the licensed vaccine is the reference for the GMT ratio, this parameter is presented as "1" for the Licensed IIV group (ie, Licensed IIV group/Licensed IIV group). |
| Solicited Local or Systemic AEs | Day 1 through Day 7 | Number and percentage of subjects with solicited local or systemic AEs for 7 days following vaccination, based on the subject reported data (electronic Diary \[eDiary\]). No hypothesis testing was performed for the primary safety objectives. |
| Severe Solicited Local or Systemic AEs | Day 1 through Day 7 | Number and percentage of subjects with severe solicited local or systemic AEs for 7 days following vaccination, based on the subject reported data (eDiary). |
| Unsolicited AEs | Day 1 to Day 29 | Number and percentage of subjects with unsolicited AEs for 28 days following vaccination |
| Subjects With Serious Adverse Events (SAEs), AEs Leading to Withdrawal, Adverse Events of Special Interest (AESIs) and Medically-attended Adverse Events (MAAEs) | Day 1 to Day 181 | Number and percentage of subjects with SAEs, AEs leading to withdrawal from the study, AESIs and non-serious MAAEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity Endpoint: GMT: Geometric Mean of Microneutralization (MN) Antibodies Titer at Days 1 and 29 | Day 1 and Day 29 | GMTs on Day 1 (prior to vaccination) and Day 29 as determined by MN assay against each of the 4 vaccine strains. |
| Immunogenicity Endpoint: GMFI (MN Assay) | Day 1 to Day 29 | Geometric mean of the fold increase in serum MN titer postvaccination (Day 29) compared to prevaccination (Day 1) for each of the 4 vaccine strains. |
| Immunogenicity Endpoint: Percentages of Subjects With Seroconversion at Day 29 (MN Assay) | Day 1 to Day 29 | Seroconversion is defined as ≥4-fold increase for subjects with prevaccination MN titers ≥LLOQ (1:10) or as ≥4\*LLOQ (1:10) for subjects with prevaccination MN titer \<LLOQ. |
| Immunogenicity Endpoint: GMT Ratio (MN Assay) | Day 29 | The GMT ratio is the geometric mean of the postvaccination HI titer for the investigational vaccine over the geometric mean of the postvaccination HI titer for the licensed IIV vaccine. The Day 29 GMT ratios are calculated for the investigational vaccines with reference to the licensed vaccine, ie, the Day 29 GMT ratios are the ratio of the Day 29 GMTs in the Investigational group (IIV-A Investigational, aIIV-B Investigational, or aIIV-C Investigational) compared with the Day 29 GMTs in the Licensed IIV group (ie, Investigational group/Licensed IIV group). As the licensed vaccine is the reference for the GMT ratio, this parameter is presented as "1" for the Licensed IIV group (ie, Licensed IIV group/Licensed IIV group). |
Countries
United States
Contacts
STUDY_DIRECTORClinical Program Director
Seqirus
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 8.63 |
| Age, Customized 50 to 64 years | 550 Participants |
| Age, Customized ≥65 years | 506 Participants |
| Body mass index | 30.35 kg/m^2 STANDARD_DEVIATION 6.552 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 243 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants |
| Race/Ethnicity, Customized Asian | 10 Participants |
| Race/Ethnicity, Customized Black or African American | 151 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Race/Ethnicity, Customized White | 884 Participants |
| Sex: Female, Male Female | 612 Participants |
| Sex: Female, Male Male | 444 Participants |
| Vaccinated within 3 previous influenza seasons No | 75 Participants |
| Vaccinated within 3 previous influenza seasons Yes | 760 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 264 | 0 / 263 | 1 / 262 | 0 / 262 |
| other Total, other adverse events | 161 / 264 | 162 / 263 | 190 / 262 | 141 / 262 |
| serious Total, serious adverse events | 8 / 264 | 5 / 263 | 4 / 262 | 10 / 262 |
Outcome results
None listed