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

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

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Flublok Quadrivalent Influenza Vaccine; Biological: Inactivated Influenza Vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 9003
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Clinical Research Consortium Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Center for Clinical Research
  • California
    • Redding, California, United States, 96001
      • Northern California Clinical Research Center
    • Sacramento, California, United States, 95816
      • Benchmark Research - Sacramento
    • San Francisco, California, United States, 94102
      • Benchmark Research - San Francisco
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Lynn Institute Of The Rockies
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Clinical Research Consulting
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research
    • Jacksonville, Florida, United States, 32205
      • Westside Center for Clinical Research
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Meridian Research
  • Idaho
    • Meridian, Idaho, United States, 83642
      • ACR - Boise
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Benchmarch Research - New Orleans
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Center for Pharmaceutical Research
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • Meridian Research
    • Norfolk, Nebraska, United States, 68701
      • Meridian Research
    • Omaha, Nebraska, United States, 68164
      • Meridian Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Clinical Research Consortium-Nevada
  • New Hampshire
    • Newington, New Hampshire, United States, 03801
      • ActivMed Practices & Research
  • New York
    • Endwell, New York, United States, 13760
      • Regional Clinical Research, Inc.
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research, Inc.
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Lynn Institute of Norman
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • South Dakota
    • Dakota Dunes, South Dakota, United States, 57049
      • Meridian Research
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates
  • Texas
    • Austin, Texas, United States, 78705
      • Benchmark Reseach
    • Fort Worth, Texas, United States, 76135
      • Benchmark Research - Fort Worth
    • San Angelo, Texas, United States, 76904
      • Benchmark Research - San Angelo
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Jean Brown Research
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Clinical Research Associates of Tidewater

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Biological: Flublok Quadrivalent Influenza Vaccine; Intramuscular injection of vaccine
Active Comparator: Inactivated Influenza Vaccine; 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; Intramuscular injection of vaccine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Protein Sciences Corporation

Publications and helpful links

General Publications

• Dunkle LM, Izikson R, Patriarca P, Goldenthal KL, Muse D, Callahan J, Cox MMJ; PSC12 Study Team. Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older. N Engl J Med. 2017 Jun 22;376(25):2427-2436. doi: 10.1056/NEJMoa1608862.

Helpful Links

• Flublok Influenza Vaccine

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: October 27, 2014
• First Submitted That Met QC Criteria: November 4, 2014
• First Posted (Estimate): November 7, 2014

Study Record Updates

• Last Update Posted (Actual): October 27, 2017
• Last Update Submitted That Met QC Criteria: September 26, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Influenza
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: PSC12