Safety and Immunogenicity of Flublok Quadrivalent vs IIV4 in Adults 18-49 Years of Age

Study Overview
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Brief Summary
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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
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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.

Official Title
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Double-Blind, Randomized, Active-Controlled Comparison of the Immunogenicity and Safety of Flublok® Quadrivalent Versus IIV4 in Healthy, Medically Stable Adults 18-49 Years of Age

Conditions
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Influenza

Intervention / Treatment
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* Biological: Flublok Quadrivalent
* Biological: Inactivated Influenza Vaccine (IIV4)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Flublok Quadrivalent Influenza Vaccine<br>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 | Biological: Flublok Quadrivalent<br>* Intramuscular injection of study vaccine<br>|
| Active Comparator: Inactivated Influenza Vaccine (IIV4)<br>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. | Biological: Inactivated Influenza Vaccine (IIV4)<br>* Intramuscular injection of study vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 28 after final vaccination | 
| 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. | Day 0 and Day 28 after final vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |