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

Phase 3
Completed
Conditions
Influenza
Interventions
Biological: Inactivated Influenza Vaccine
Biological: Flublok Quadrivalent Influenza Vaccine
Registration Number
NCT02285998
Lead Sponsor
Protein Sciences Corporation
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
9003
Inclusion Criteria
  1. Ambulatory adults aged 50 and older.
  2. 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.
  3. Absence of underlying conditions that make participation in the study contrary to the subject's best interest.
  4. Able to understand and comply with planned study procedures.
  5. Provides written informed consent prior to initiation of any study procedure.
Exclusion Criteria
  1. Known contraindication to either study vaccine (see product package inserts)
  2. Receipt of any other influenza vaccine within 180 days prior to enrollment in this study.
  3. 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Inactivated Influenza VaccineInactivated Influenza VaccineIntramuscular 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.
Flublok Quadrivalent Influenza VaccineFlublok Quadrivalent Influenza VaccineIntramuscular 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
Primary Outcome Measures
NameTimeMethod
Number of Participants With rtPCR-confirmed Influenza-Like Illness14 days post vaccination through and up to 32 weeks post vaccination

rtPCR-confirmed, protocol-defined Influenza-Like Illness (ILI) caused by any influenza strain that begins at least 14 days post-vaccination

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Culture-confirmed Influenza-Like Illness14 days post vaccination through and up to 32 weeks post vaccination

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)

Number of Participants With Culture-confirmed CDC-defined Influenza-Like Illness14 days post vaccination through and up to 32 weeks post vaccination

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.

Number of Participants With rtPCR-confirmed CDC-defined Influenza-Like Illness14 days post vaccination through and up to 32 weeks post vaccination

rtPCR-confirmed CDC-defined ILI that begins at least 14 days post-vaccination caused by any influenza strain.

Percentage of Participants With SeroconversionDays 0 through 28

Seroconversion rates (SCR) for all four antigens in a preselected subset of subjects.

Number of Participants With Local Injection Site ReactogenicityDays 0 through 7

Solicited events of injection site reactogenicity reported during Day 0-7.

Number of Participants With Unsolicited Adverse EventsDays 0 through 28

Unsolicited adverse events reported in the 28 days following vaccine administration.

Number of Participants With Serious Adverse Events (SAEs) and Medically-attended Adverse Events (MAEs)Day 0 through and up to 32 weeks post vaccination

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.

Measure of Post-vaccination HAI GMTsDays 0 through 28

GMT titers for all four antigens in a preselected subset of subjects.

Number of Participants With Systemic ReactogenicityDays 0 through 7

Solicited events of systemic reactogenicity reported during Day 0-7.

Trial Locations

Locations (34)

Wake Research

🇺🇸

Raleigh, North Carolina, United States

Jean Brown Research

🇺🇸

Salt Lake City, Utah, United States

Lynn Institute of the Rockies

🇺🇸

Colorado Springs, Colorado, United States

Clinical Research Associates

🇺🇸

Nashville, Tennessee, United States

Clinical Research Consulting

🇺🇸

Milford, Connecticut, United States

Clinical Research Consortium-Nevada

🇺🇸

Las Vegas, Nevada, United States

Coastal Clinical Research

🇺🇸

Mobile, Alabama, United States

Northern California Clinical Research Center

🇺🇸

Redding, California, United States

ACR - Boise

🇺🇸

Meridian, Idaho, United States

ActivMed Practices & Research

🇺🇸

Newington, New Hampshire, United States

Clinical Research Consortium Arizona

🇺🇸

Tempe, Arizona, United States

Lynn Institute of Norman

🇺🇸

Norman, Oklahoma, United States

Benchmark Research - San Francisco

🇺🇸

San Francisco, California, United States

Baptist Health Center for Clinical Research

🇺🇸

Little Rock, Arkansas, United States

Clinical Research of South Florida

🇺🇸

Coral Gables, Florida, United States

Westside Center for Clinical Research

🇺🇸

Jacksonville, Florida, United States

Benchmark Research - Fort Worth

🇺🇸

Fort Worth, Texas, United States

Benchmarch Research - New Orleans

🇺🇸

Metairie, Louisiana, United States

Regional Clinical Research, Inc.

🇺🇸

Endwell, New York, United States

Lynn Health Science Institute

🇺🇸

Oklahoma City, Oklahoma, United States

Central Kentucky Research Associates

🇺🇸

Lexington, Kentucky, United States

Rapid Medical Research, Inc.

🇺🇸

Cleveland, Ohio, United States

Clinical Research Associates of Tidewater

🇺🇸

Norfolk, Virginia, United States

Rochester Clinical Research

🇺🇸

Rochester, New York, United States

Benchmark Reseach

🇺🇸

Austin, Texas, United States

Benchmark Research - Sacramento

🇺🇸

Sacramento, California, United States

Avail Clinical Research

🇺🇸

DeLand, Florida, United States

Jacksonville Center for Clinical Research

🇺🇸

Jacksonville, Florida, United States

Progressive Medical Research

🇺🇸

Port Orange, Florida, United States

Center for Pharmaceutical Research

🇺🇸

Kansas City, Missouri, United States

Benchmark Research - San Angelo

🇺🇸

San Angelo, Texas, United States

Meridian Research

🇺🇸

Dakota Dunes, South Dakota, United States

Heartland Research Associates, LLC

🇺🇸

Wichita, Kansas, United States

Meridian Clinical Research

🇺🇸

Omaha, Nebraska, United States

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