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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02285998
Recruitment Status : Completed
First Posted : November 7, 2014
Results First Posted : October 4, 2016
Last Update Posted : October 27, 2017
Sponsor:
Information provided by (Responsible Party):
Protein Sciences Corporation

Tracking Information
First Submitted Date  ICMJE October 27, 2014
First Posted Date  ICMJE November 7, 2014
Results First Submitted Date  ICMJE August 3, 2016
Results First Posted Date  ICMJE October 4, 2016
Last Update Posted Date October 27, 2017
Study Start Date  ICMJE October 2014
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2014)
Number of Participants With rtPCR-confirmed Influenza-Like Illness [ Time Frame: 14 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
  • Number of Participants With Culture-confirmed Influenza-Like Illness [ Time Frame: 14 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 Illness [ Time Frame: 14 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 Illness [ Time Frame: 14 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 Seroconversion [ Time Frame: Days 0 through 28 ]
    Seroconversion rates (SCR) for all four antigens in a preselected subset of subjects.
  • Number of Participants With Local Injection Site Reactogenicity [ Time Frame: Days 0 through 7 ]
    Solicited events of injection site reactogenicity reported during Day 0-7.
  • Number of Participants With Unsolicited Adverse Events [ Time Frame: Days 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) [ Time Frame: 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 GMTs [ Time Frame: Days 0 through 28 ]
    GMT titers for all four antigens in a preselected subset of subjects.
  • Number of Participants With Systemic Reactogenicity [ Time Frame: Days 0 through 7 ]
    Solicited events of systemic reactogenicity reported during Day 0-7.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2014)
  • Number of Participants With Culture-confirmed Influenza-Like Illness [ Time Frame: 14 days post vaccination through and up to 32 weeks post vaccination ]
    Culture-confirmed protocol-defined 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.
  • Number of Participants With Culture-confirmed CDC-defined Influenza-Like Illness [ Time Frame: 14 days post vaccination through and up to 32 weeks post vaccination ]
    Culture-confirmed CDC-defined 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.
  • Number of Participants With rtPCR-confirmed CDC-defined Influenza-Like Illness [ Time Frame: 14 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.
  • Number of Participants with seroconversion [ Time Frame: Days 0 through 28 ]
    Post-vaccination HAI GMTs and seroconversion rates (SCR) for all four antigens in a preselected subset of subjects.
  • Number of Participants with Systemic and injection site reactogenicity [ Time Frame: Days 0 through 7 ]
    Solicited events of systemic and injection site reactogenicity reported during Day 0-7.
  • Number of Participants With Unsolicited Adverse Events [ Time Frame: Days 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) [ Time Frame: 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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Protective Efficacy of Flublok® Quadrivalent Versus Licensed Inactivated Influenza Vaccine in Adults ≥50 Years of Age
Official Title  ICMJE Comparison of the Protective Efficacy of Flublok® Quadrivalent Versus Licensed Inactivated Influenza Vaccine (IIV4) in Healthy, Medically Stable Adults ≥50 Years of Age
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Influenza
Intervention  ICMJE
  • Biological: Flublok Quadrivalent Influenza Vaccine
    Intramuscular injection of vaccine
  • Biological: Inactivated Influenza Vaccine
    Intramuscular injection of vaccine
Study Arms  ICMJE
  • 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
    Intervention: Biological: Flublok Quadrivalent Influenza 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.
    Intervention: Biological: Inactivated Influenza Vaccine
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 10, 2016)
9003
Original Estimated Enrollment  ICMJE
 (submitted: November 4, 2014)
9000
Actual Study Completion Date  ICMJE May 2015
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02285998
Other Study ID Numbers  ICMJE PSC12
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Protein Sciences Corporation
Study Sponsor  ICMJE Protein Sciences Corporation
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Protein Sciences Corporation
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP