Protective Efficacy of Flublok® Quadrivalent Versus Licensed Inactivated Influenza Vaccine in Adults ≥50 Years of Age

Study Overview
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Brief Summary
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The goal of this study is to establish that Flublok Quadrivalent is non-inferior to fully licensed (traditional approval status) quadrivalent inactivated influenza vaccine (IIV4) in protecting against laboratory-confirmed clinical influenza disease in the ≥50 year age population.

Detailed Description
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The goal of this study is to establish that Flublok Quadrivalent is non-inferior to fully licensed (traditional approval status) quadrivalent inactivated influenza vaccine (IIV4) in protecting against laboratory-confirmed clinical influenza disease in the ≥50 year age population. Real-time Polymerase Chain Reaction (rtPCR) will be used to confirm influenza infection and to type the strains involved, as molecular methodologies have been demonstrated to be more sensitive than other more traditional methodologies, e.g. culture. For rtPCR-positive clinical samples, reserved aliquots will be processed for culture, so that antigenic similarity to the HA present in study vaccines can be tested. In various clinical studies the investigators demonstrated that the immune response against the influenza A viruses is improved as a result of the higher hemagglutinin content. Furthermore, influenza virus disease and hospitalization associated with influenza-related illness in older adults (> 50 years) was considerably reduced (90%) following vaccination with TIV, even though the circulating influenza A strain was antigenically dissimilar to that in the vaccine. However, more recently Skowronski et al. reported that the low influenza vaccine effectiveness in 2012-2013 was not associated with antigenic drift but was instead related to mutations in the egg-adapted H3N2 vaccine strain. Flublok manufactured using recombinant technology does not contain the mutations responsible for the reported lower effectiveness and may thus offer improved protection when mutations such as those described are induced in the process of adapting the influenza virus to growth in eggs.

Official Title
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Comparison of the Protective Efficacy of Flublok® Quadrivalent Versus Licensed Inactivated Influenza Vaccine (IIV4) in Healthy, Medically Stable Adults ≥50 Years of Age

Conditions
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Influenza

Intervention / Treatment
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* Biological: Flublok Quadrivalent Influenza Vaccine
* Biological: Inactivated Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory adults aged 50 and older. Medically stable, as determined by medical history and targeted physical examination. Medically stable is defined as no change in diagnoses or chronic medications (dose or class) for medical reasons in the 3 months prior to study. Absence of underlying conditions that make participation in the study contrary to the subject's best interest. Able to understand and comply with planned study procedures. Provides written informed consent prior to initiation of any study procedure. Exclusion Criteria: Known contraindication to either study vaccine (see product package inserts) Receipt of any other influenza vaccine within 180 days prior to enrollment in this study. Underlying disease or ongoing therapy that might cause immunocompromise, e.g. cytotoxic agents or supraphysiologic doses of corticosteroids, such that response to vaccination might be sub-optimal.

Ages Eligible for Study
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Minimum Age: 50 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 Influenza Vaccine<br>* Intramuscular injection of vaccine<br>|
| Active Comparator: Inactivated Influenza Vaccine<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<br>* Intramuscular injection of vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With rtPCR-confirmed Influenza-Like Illness | rtPCR-confirmed, protocol-defined Influenza-Like Illness (ILI) caused by any influenza strain that begins at least 14 days post-vaccination | 14 days post vaccination through and up to 32 weeks post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Culture-confirmed Influenza-Like Illness | Culture-confirmed protocol-defined Influenza-Like Illness (ILI) that begins at least 14 days post-vaccination caused by an influenza strain (identified from the same clinical sample) antigenically matched to those strains represented in the study vaccines. Protocol-defined ILI is defined as at least one of the following respiratory symptoms accompanied by at least one of the following systemic symptoms: Respiratory symptoms: sore throat, cough, sputm production, wheezing, difficulty breathing Systemic symptoms: fever, chills (shivering), tiredness (fatigue), headache, myalgia (muscle ache) | 14 days post vaccination through and up to 32 weeks post vaccination | 
| Number of Participants With Culture-confirmed CDC-defined Influenza-Like Illness | Culture-confirmed CDC-defined Influenza-Like Illness (ILI) that begins at least 14 days post-vaccination caused by an influenza strain (identified from the same clinical sample) antigenically matched to those in the study vaccines. CDC-defined ILI is defined as body temperature ≥100°F accompanied by cough and/or sore throat. | 14 days post vaccination through and up to 32 weeks post vaccination | 
| Number of Participants With rtPCR-confirmed CDC-defined Influenza-Like Illness | rtPCR-confirmed CDC-defined ILI that begins at least 14 days post-vaccination caused by any influenza strain. | 14 days post vaccination through and up to 32 weeks post vaccination | 
| Percentage of Participants With Seroconversion | Seroconversion rates (SCR) for all four antigens in a preselected subset of subjects. | Days 0 through 28 | 
| Number of Participants With Local Injection Site Reactogenicity | Solicited events of injection site reactogenicity reported during Day 0-7. | Days 0 through 7 | 
| Number of Participants With Unsolicited Adverse Events | Unsolicited adverse events reported in the 28 days following vaccine administration. | Days 0 through 28 | 
| Number of Participants With Serious Adverse Events (SAEs) and Medically-attended Adverse Events (MAEs) | Serious adverse events (SAEs) and medically-attended adverse events (MAEs) occurring during the period of follow-up through the influenza season (at least 6 months post-vaccination). A MAE is an event that prompts an unplanned visit to a medical professional for diagnosis and/or treatment. | Day 0 through and up to 32 weeks post vaccination | 
| Measure of Post-vaccination HAI GMTs | GMT titers for all four antigens in a preselected subset of subjects. | Days 0 through 28 | 
| Number of Participants With Systemic Reactogenicity | Solicited events of systemic reactogenicity reported during Day 0-7. | Days 0 through 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza