Influenza
Conditions
Brief summary
Randomized, double-blind trial of safety and immunogenicity of Flublok Quadrivalent versus Inactivated Influenza Vaccine (IIV4) in 1350 healthy, medically stable adults 18-49 years of age. Serum samples for Hemagglutinin Inhibition titers will be determined pre- and 28 days post-vaccination. Subjects will be followed for 6 months after vaccination for serious and/or medically-attended adverse events.
Detailed description
As the spectrum of influenza vaccines rapidly evolves to quadrivalent formulations with the intention of offering broader protection to include both lineages of influenza B strains, it is appropriate to transition Flublok from a trivalent to a quadrivalent formulation. The demonstration of non-inferior post-vaccination Hemagglutination Inhibition Assay (HAI) Geometric Mean Titers (GMTs) to antigens in the Flublok Quadrivalent formulation compared to those of the matching antigens in a US - approved IIV4 is intended to support licensure of Flublok Quadrivalent for the adult population for which Flublok trivalent is currently approved. The comparison of safety and reactogenicity of Flublok Quadrivalent to that of IIV4 is expected to confirm a similar safety profile.
Interventions
BIOLOGICALFlublok Quadrivalent
Intramuscular injection of study vaccine
BIOLOGICALInactivated Influenza Vaccine (IIV4)
Intramuscular injection of study vaccine
Sponsors
Syneos Health
Department of Health and Human Services
Protein Sciences Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Ambulatory, in good health or medically stable * Able to understand and comply with planned study procedures * Provide written informed consent * Negative urine pregnancy test within 24 hours prior to vaccination (women of child-bearing potential)
Exclusion criteria
* Prior serious or severe reaction to influenza vaccine * Known contraindication to either study vaccine * Receipt of any other influenza vaccine within 180 days prior to enrollment * Plan to receive another licensed influenza or other vaccine during the duration of this study * Receipt of any significant new diagnosis, medication (licensed or investigational), or licensed vaccine within 30 days prior to enrollment in this study * Underlying disease or therapeutic intervention that might adversely affect the immune response * Plans to participate in any investigation involving an investigational product during this study. * Pregnant, lactating or planning to become pregnant within 30 days of study vaccine. * Any clinical or social circumstance that in the opinion of the investigator could interfere with compliance with study procedures or interfere with the interpretation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 28 after final vaccination | Seroconversion is defined as: Either a pre vaccination titer \< 10 (1/dil) and a post vaccination titer ≥ 40 (1/dil), or a pre vaccination titer ≥ 10 (1/dil) and a ≥ 4 fold increase in post vaccination titer at Day 28 after the final vaccination. |
| Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 0 and Day 28 after final vaccination | Immunogenicity will be evaluated prior to vaccination and at 28 days after vaccination using the hemagglutination inhibition (HAI) technique. For each influenza vaccine strain, pre and post vaccination geometric mean titers (GMTs) were calculated. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Systemic and Injection Site Reactogenicity | Days 0-7 |
| Number of Participants With Serious Adverse Events (SAEs) and Medically-attended Adverse Events (MAEs) | Six months post-vaccination |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Flublok Quadrivalent Influenza Vaccine Intramuscular injection of vaccine containing 4 x 45µg (180µg total) of each recombinant hemagglutinin (rHA) derived from influenza A/H1N1 and A/H3N2 and two lineages of influenza B viruses identified for the season in which the trial is conducted in a total volume of 0.5 mL
Flublok Quadrivalent: Intramuscular injection of study vaccine | 998 |
| Inactivated Influenza Vaccine (IIV4) Intramuscular injection of vaccine contains 4 x 15µg (60µg total) of HA derived from the same influenza A/H1N1 and A/H3N2 and influenza B strains in a total volume of 0.5mL.
Inactivated Influenza Vaccine (IIV4): Intramuscular injection of study vaccine | 332 |
| Total | 1,330 |
Baseline characteristics
| Characteristic | Flublok Quadrivalent Influenza Vaccine | Inactivated Influenza Vaccine (IIV4) | Total |
|---|---|---|---|
| Age, Customized 18-49 years | 998 participants | 332 participants | 1330 participants |
| Region of Enrollment United States | 998 participants | 332 participants | 1330 participants |
| Sex: Female, Male Female | 639 Participants | 222 Participants | 861 Participants |
| Sex: Female, Male Male | 359 Participants | 110 Participants | 469 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 63 / 998 | 24 / 332 |
| serious Total, serious adverse events | 10 / 998 | 2 / 332 |
Outcome results
Primary
Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine
Immunogenicity will be evaluated prior to vaccination and at 28 days after vaccination using the hemagglutination inhibition (HAI) technique. For each influenza vaccine strain, pre and post vaccination geometric mean titers (GMTs) were calculated.
Time frame: Day 0 and Day 28 after final vaccination
Population: The immunogenicity population includes all randomized subjects who received a dose of study vaccine, provided serum samples for baseline (Day 0) and Day 28 HAI titers (within the specified windows) and have no major protocol deviations that might have adversely affect the immune response.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Flublok Quadrivalent Influenza Vaccine | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 0 - B/Massachusetts | 27 titer |
| Flublok Quadrivalent Influenza Vaccine | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 28 - B/Brisbane | 43 titer |
| Flublok Quadrivalent Influenza Vaccine | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 0 - A/H1N1/California | 60 titer |
| Flublok Quadrivalent Influenza Vaccine | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 28 - A/H1N1/California | 502 titer |
| Flublok Quadrivalent Influenza Vaccine | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 0 - A/H3N2/Texas | 75 titer |
| Flublok Quadrivalent Influenza Vaccine | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 28 - A/H3N2/Texas | 757 titer |
| Flublok Quadrivalent Influenza Vaccine | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 28 - B/Massachusetts | 159 titer |
| Flublok Quadrivalent Influenza Vaccine | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 0 - B/Brisbane | 12 titer |
| Inactivated Influenza Vaccine (IIV4) | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 0 - B/Brisbane | 11 titer |
| Inactivated Influenza Vaccine (IIV4) | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 0 - B/Massachusetts | 24 titer |
| Inactivated Influenza Vaccine (IIV4) | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 28 - B/Brisbane | 64 titer |
| Inactivated Influenza Vaccine (IIV4) | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 0 - A/H3N2/Texas | 70 titer |
| Inactivated Influenza Vaccine (IIV4) | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 28 - B/Massachusetts | 136 titer |
| Inactivated Influenza Vaccine (IIV4) | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 0 - A/H1N1/California | 54 titer |
| Inactivated Influenza Vaccine (IIV4) | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 28 - A/H3N2/Texas | 385 titer |
| Inactivated Influenza Vaccine (IIV4) | Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Day 28 - A/H1N1/California | 407 titer |
Primary
Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine
Seroconversion is defined as: Either a pre vaccination titer \< 10 (1/dil) and a post vaccination titer ≥ 40 (1/dil), or a pre vaccination titer ≥ 10 (1/dil) and a ≥ 4 fold increase in post vaccination titer at Day 28 after the final vaccination.
Time frame: Day 28 after final vaccination
Population: The immunogenicity population includes all randomized subjects who received a dose of study vaccine, provided serum samples for baseline (Day 0) and Day 28 HAI titers (within the specified windows) and have no major protocol deviations that might have adversely affect the immune response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flublok Quadrivalent Influenza Vaccine | Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | A/H1N1/California | 66.7 percentage of participants |
| Flublok Quadrivalent Influenza Vaccine | Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | A/H3N2/Texas | 72.1 percentage of participants |
| Flublok Quadrivalent Influenza Vaccine | Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | B/Massachusetts | 59.6 percentage of participants |
| Flublok Quadrivalent Influenza Vaccine | Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | B/Brisbane | 40.6 percentage of participants |
| Inactivated Influenza Vaccine (IIV4) | Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | B/Brisbane | 58.2 percentage of participants |
| Inactivated Influenza Vaccine (IIV4) | Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | A/H1N1/California | 63.5 percentage of participants |
| Inactivated Influenza Vaccine (IIV4) | Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | B/Massachusetts | 60.4 percentage of participants |
| Inactivated Influenza Vaccine (IIV4) | Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | A/H3N2/Texas | 57.0 percentage of participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs) and Medically-attended Adverse Events (MAEs)
Time frame: Six months post-vaccination
Population: The safety population includes all randomized and vaccinated subjects who provided any safety data (solicited or unsolicited) following administration of study vaccine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flublok Quadrivalent Influenza Vaccine | Number of Participants With Serious Adverse Events (SAEs) and Medically-attended Adverse Events (MAEs) | Serious adverse events (SAEs) | 10 participants |
| Flublok Quadrivalent Influenza Vaccine | Number of Participants With Serious Adverse Events (SAEs) and Medically-attended Adverse Events (MAEs) | Medically-attended adverse events (MAEs) | 80 participants |
| Inactivated Influenza Vaccine (IIV4) | Number of Participants With Serious Adverse Events (SAEs) and Medically-attended Adverse Events (MAEs) | Serious adverse events (SAEs) | 2 participants |
| Inactivated Influenza Vaccine (IIV4) | Number of Participants With Serious Adverse Events (SAEs) and Medically-attended Adverse Events (MAEs) | Medically-attended adverse events (MAEs) | 24 participants |
Secondary
Number of Participants With Systemic and Injection Site Reactogenicity
Time frame: Days 0-7
Population: The Reactogenicity Population includes subjects who recorded any systemic reaction data and injection site reaction data following administration of study vaccine. This was two subjects less than the Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flublok Quadrivalent Influenza Vaccine | Number of Participants With Systemic and Injection Site Reactogenicity | Subjects with one or more injection site reaction | 510 participants |
| Flublok Quadrivalent Influenza Vaccine | Number of Participants With Systemic and Injection Site Reactogenicity | Subjects with one or more systemic reaction event | 339 participants |
| Inactivated Influenza Vaccine (IIV4) | Number of Participants With Systemic and Injection Site Reactogenicity | Subjects with one or more injection site reaction | 172 participants |
| Inactivated Influenza Vaccine (IIV4) | Number of Participants With Systemic and Injection Site Reactogenicity | Subjects with one or more systemic reaction event | 119 participants |