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Live Attenuated Influenza Vaccine (LAIV) Versus Trivalent Inactivated Influenza Vaccine in Healthy Adults 18-49 Years

Primary Purpose

Influenza

Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Inactivated Influenza Vaccine
Live Attenuated Influenza Vaccine
Sponsored by
St. Louis University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza

Eligibility Criteria

18 Years - 49 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Male or female age 18 to 49 years, inclusive, on the day of randomization (reached his or her 18th year birthday but not yet reached his or her 50th year birthday) at the time of the dose of study product
  • Written informed consent and a locally required authorization (eg, HIPAA in the USA, ) obtained from the subject prior to performing any protocol-related procedures.
  • Females of child-bearing potential, (ie, unless surgically sterile [eg, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy], has sterile male partner, is at least 1 year post-menopausal, or practices abstinence) must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, or use of a condom with spermicide by the sexual partner) for 30 days prior to the first dose of study product, and must agree to continue using such precautions for 60 days after the dose of vaccine due to a potential dose of live vaccine product. In addition, the subject must also have a negative urine or blood pregnancy test at screening and, if screening and Day 0 do not occur on the same day, a negative urine pregnancy test on the day of vaccination prior to randomization. Investigator judgment is required to assess a female subject's capability of pregnancy.
  • Are in good health, as determined by vital signs, medical history to ensure any existing medical diagnoses or conditions are stable and not considered clinically significant by physician investigator, and targeted physical examination based on medical history.
  • Able to complete follow-up period of 180 days post dose of vaccine as required by the protocol
  • Subject available by telephone
  • Able to understand and comply with the requirements of the protocol, as judged by the investigator

Exclusion Criteria:

Any of the following would exclude the subject from participation in the study:

  • Have an acute illness, including an oral temperature ≥ 100.4°F, within 3 days prior to vaccination.
  • Participated in an investigational influenza vaccine study or had a known infection with "flu" since 2007 (confirmed by laboratory culture, including subtype of the influenza A virus (H1N1) investigational vaccines or illness).
  • Previous vaccination against influenza in 2007, 2008, 2009 or 2010 with seasonal trivalent live or inactivated influenza vaccine (including H1N1 vaccines).
  • Current or expected receipt of immunosuppressive medications (inhaled and topical corticosteroids are permitted) including corticosteroids (≥ 20 mg/day of prednisone equivalent given daily or on alternate days for ≥ 14 days) within a 30 day window around dose of study vaccine product Note: topical corticosteroids for uncomplicated dermatitis may be used throughout the study according to the judgment of the investigator; topical calcineurin inhibitors may be used in accordance with their package insert at entry and during study participation.
  • Receipt of immunoglobulin or blood products within 90 days before randomization into the study or expected receipt during study participation
  • Received an experimental agent within 1 month prior to vaccination in this study or expect to receive an experimental agent during the active study period (prior to Day 60 after vaccination (Experimental agent includes: vaccine, biologic, device, or medication).
  • Have received any live licensed vaccines within 4 weeks or inactivated licensed vaccines within 2 weeks prior to vaccination in this study or plan receipt of such vaccines within 60 days following the vaccination.
  • Any known immunosuppressive condition or immune deficiency disease including known cancer illness or organ transplant
  • Have known active HIV, Hepatitis B or Hepatitis C infection.
  • Have a known allergy to eggs or other components of the vaccine (including gelatin, formaldehyde, octoxinol, thimerosal, gentamycin and chicken protein) or severe reactions to previous influenza vaccinations.
  • History of Guillain-Barré syndrome
  • Use of antiviral agents with activity against influenza virus (including amantadine, rimantadine, oseltamivir and zanamivir) within 30 days prior to dose of study vaccine products or anticipated use within 30 days after vaccination
  • Breastfeeding woman
  • History of alcohol or drug abuse that, in the opinion of the investigator, would affect the subject's safety or compliance with study
  • Previous medical history, evidence of an intercurrent illness or any condition that, in the opinion of the investigator, would interfere with evaluation of the study vaccine products or interpretation of subject safety or that may compromise the safety of the subject in the study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Active Comparator

    Arm Label

    Group 1

    Group 2

    Arm Description

    One dose of 0.5 mL Licensed Inactivated Influenza Vaccine (IIV) on Day 0

    One dose of 0.5 mL Licensed Live Attenuated Influenza Vaccine (LAIV) on Day 0

    Outcomes

    Primary Outcome Measures

    Serum Antibody Responses
    Geometric mean hemagglutination inhibition titers to three different influenza viruses
    T-cell Responses
    Number of Interferon gamma ELISPOT spot forming cells (SFC) per million Peripheral Blood Mononuclear Cells (PBMCs) were calculated.
    Cluster of Differentiation 4 (CD4+) T Cells That Proliferate and Produce Interferon (IFN)-Gamma After Antigen Activation
    Mean absolute numbers of CD4(+), Carboxyfluorescein succinimidyl ester [CFSE(low)] IFN-gamma(+), and T cells after activation with a specific antigen measured by flow cytometry
    Secretory Immunoglobulin A (IgA) Responses
    Influenza virus strain-specific nasal wash secretory immunoglobulin A (IgA) titers by ELISA was measured
    Hemagglutinin Immunoglobulin A (IgA) Responses
    Hemagglutinin (HA) specific nasal wash secretory immunoglobulin A (IgA) of serum reactivity with HA bound to ELISA plates.

    Secondary Outcome Measures

    Full Information

    First Posted
    March 23, 2017
    Last Updated
    November 6, 2018
    Sponsor
    St. Louis University
    Collaborators
    MedImmune LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03101462
    Brief Title
    Live Attenuated Influenza Vaccine (LAIV) Versus Trivalent Inactivated Influenza Vaccine in Healthy Adults 18-49 Years
    Official Title
    A Randomized, Open-Label, Study to Evaluate the Immunogenicity of One Dose of Live Attenuated Influenza Vaccine (LAIV) Compared to One Dose of Trivalent Inactivated Influenza Vaccine (IIV) in Adults 18-49 Years of Age
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    February 24, 2011 (Actual)
    Primary Completion Date
    May 13, 2011 (Actual)
    Study Completion Date
    November 9, 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    St. Louis University
    Collaborators
    MedImmune LLC

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This randomized, open-label, single-site study at Saint Louis University will enroll approximately 40 subjects who are healthy, 18 to 49 years old. Subjects will be randomized in a 1:1 fashion to receive either licensed trivalent FluMist containing (2010-2011 season appropriate), or licensed inactivated trivalent influenza vaccine (2010-2011 season appropriate) so that approximately 20 subjects will be randomized to receive LAIV, and 20 will receive IIV.
    Detailed Description
    This Phase IV, randomized, open-label, single-site study at Saint Louis University will enroll approximately 40 subjects who are healthy, 18 to 49 years old. Subjects will be randomized in a 1:1 fashion to receive either licensed inactivated influenza vaccine (IIV) (2010-2011 season appropriate) or licensed live attenuated influenza vaccine (LAIV) (2010-2011 season appropriate) so that approximately 20 subjects will be randomized to receive IIV, and 20 will receive LAIV. Subjects will receive 1 dose of IIV or LAIV in the Center for Vaccine Development on Day 0 and will return to the site on days 7 and 45 to assess immunogenicity. Subjects will be asked to report any serious adverse events. Blood samples and nasal washes for assessment of immune responses will be obtained at three time points: on Day 0 prior to dosing with IIV or LAIV, and at visits conducted 7 and 45-51 days post vaccination. The study will be conducted just prior to and during the influenza season. Subjects will receive a single dose of IIV or LAIV administered as instructed per package insert. Two contacts will be made with subjects, either telephone calls or e-mail, to collect serious adverse events only, one at Days 28-35, and one at approximately Days 180-190 to conclude the subject's participation. The duration of each subject's participation is approximately 6 months. The primary immune studies conducted with collected samples will include serum hemagglutinin inhibition (HAI) antibody titers, nasal wash influenza-specific secretory immunoglobulin A (IgA) responses, peripheral blood interferon gamma (IFN-γ) ELISPOT assays and peripheral blood carboxyfluorescein succinimidyl ester (CFSE) dilution/intracellular cytokine staining flow cytometric assays. In addition, frozen serum and peripheral blood mononuclear cells (PBMC) samples will be used in exploratory assays to determine the kinetics and nature of innate responses and the detailed molecular signatures of memory T cells induced by IIV and LAIV vaccinations. Investigators will be performing genome-wide expression studies, but will not perform DNA sequencing and will not send anything other than coded samples outside of Saint Louis University.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Influenza

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Model Description
    Subjects will be randomized to one of two different groups to receive either licensed inactivated influenza vaccine (IIV) or licensed live attenuated influenza vaccine (LAIV) from the 2010-2011 season.
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    38 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Group 1
    Arm Type
    Active Comparator
    Arm Description
    One dose of 0.5 mL Licensed Inactivated Influenza Vaccine (IIV) on Day 0
    Arm Title
    Group 2
    Arm Type
    Active Comparator
    Arm Description
    One dose of 0.5 mL Licensed Live Attenuated Influenza Vaccine (LAIV) on Day 0
    Intervention Type
    Biological
    Intervention Name(s)
    Inactivated Influenza Vaccine
    Other Intervention Name(s)
    IIV
    Intervention Type
    Biological
    Intervention Name(s)
    Live Attenuated Influenza Vaccine
    Other Intervention Name(s)
    LAIV
    Primary Outcome Measure Information:
    Title
    Serum Antibody Responses
    Description
    Geometric mean hemagglutination inhibition titers to three different influenza viruses
    Time Frame
    Day 0, Day 7, and Day 45
    Title
    T-cell Responses
    Description
    Number of Interferon gamma ELISPOT spot forming cells (SFC) per million Peripheral Blood Mononuclear Cells (PBMCs) were calculated.
    Time Frame
    Day 0, Day 7, and Day 45
    Title
    Cluster of Differentiation 4 (CD4+) T Cells That Proliferate and Produce Interferon (IFN)-Gamma After Antigen Activation
    Description
    Mean absolute numbers of CD4(+), Carboxyfluorescein succinimidyl ester [CFSE(low)] IFN-gamma(+), and T cells after activation with a specific antigen measured by flow cytometry
    Time Frame
    Day 0, Day 7, and Day 45
    Title
    Secretory Immunoglobulin A (IgA) Responses
    Description
    Influenza virus strain-specific nasal wash secretory immunoglobulin A (IgA) titers by ELISA was measured
    Time Frame
    Day 0 and Day 45
    Title
    Hemagglutinin Immunoglobulin A (IgA) Responses
    Description
    Hemagglutinin (HA) specific nasal wash secretory immunoglobulin A (IgA) of serum reactivity with HA bound to ELISA plates.
    Time Frame
    Day 7

    10. Eligibility

    Sex
    All
    Gender Based
    Yes
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    49 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Male or female age 18 to 49 years, inclusive, on the day of randomization (reached his or her 18th year birthday but not yet reached his or her 50th year birthday) at the time of the dose of study product Written informed consent and a locally required authorization (eg, HIPAA in the USA, ) obtained from the subject prior to performing any protocol-related procedures. Females of child-bearing potential, (ie, unless surgically sterile [eg, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy], has sterile male partner, is at least 1 year post-menopausal, or practices abstinence) must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives, intrauterine device, female condom with spermicide, diaphragm with spermicide, cervical cap, or use of a condom with spermicide by the sexual partner) for 30 days prior to the first dose of study product, and must agree to continue using such precautions for 60 days after the dose of vaccine due to a potential dose of live vaccine product. In addition, the subject must also have a negative urine or blood pregnancy test at screening and, if screening and Day 0 do not occur on the same day, a negative urine pregnancy test on the day of vaccination prior to randomization. Investigator judgment is required to assess a female subject's capability of pregnancy. Are in good health, as determined by vital signs, medical history to ensure any existing medical diagnoses or conditions are stable and not considered clinically significant by physician investigator, and targeted physical examination based on medical history. Able to complete follow-up period of 180 days post dose of vaccine as required by the protocol Subject available by telephone Able to understand and comply with the requirements of the protocol, as judged by the investigator Exclusion Criteria: Any of the following would exclude the subject from participation in the study: Have an acute illness, including an oral temperature ≥ 100.4°F, within 3 days prior to vaccination. Participated in an investigational influenza vaccine study or had a known infection with "flu" since 2007 (confirmed by laboratory culture, including subtype of the influenza A virus (H1N1) investigational vaccines or illness). Previous vaccination against influenza in 2007, 2008, 2009 or 2010 with seasonal trivalent live or inactivated influenza vaccine (including H1N1 vaccines). Current or expected receipt of immunosuppressive medications (inhaled and topical corticosteroids are permitted) including corticosteroids (≥ 20 mg/day of prednisone equivalent given daily or on alternate days for ≥ 14 days) within a 30 day window around dose of study vaccine product Note: topical corticosteroids for uncomplicated dermatitis may be used throughout the study according to the judgment of the investigator; topical calcineurin inhibitors may be used in accordance with their package insert at entry and during study participation. Receipt of immunoglobulin or blood products within 90 days before randomization into the study or expected receipt during study participation Received an experimental agent within 1 month prior to vaccination in this study or expect to receive an experimental agent during the active study period (prior to Day 60 after vaccination (Experimental agent includes: vaccine, biologic, device, or medication). Have received any live licensed vaccines within 4 weeks or inactivated licensed vaccines within 2 weeks prior to vaccination in this study or plan receipt of such vaccines within 60 days following the vaccination. Any known immunosuppressive condition or immune deficiency disease including known cancer illness or organ transplant Have known active HIV, Hepatitis B or Hepatitis C infection. Have a known allergy to eggs or other components of the vaccine (including gelatin, formaldehyde, octoxinol, thimerosal, gentamycin and chicken protein) or severe reactions to previous influenza vaccinations. History of Guillain-Barré syndrome Use of antiviral agents with activity against influenza virus (including amantadine, rimantadine, oseltamivir and zanamivir) within 30 days prior to dose of study vaccine products or anticipated use within 30 days after vaccination Breastfeeding woman History of alcohol or drug abuse that, in the opinion of the investigator, would affect the subject's safety or compliance with study Previous medical history, evidence of an intercurrent illness or any condition that, in the opinion of the investigator, would interfere with evaluation of the study vaccine products or interpretation of subject safety or that may compromise the safety of the subject in the study.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Daniel F Hoft, MD, PhD
    Organizational Affiliation
    St. Louis University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    27847366
    Citation
    Hoft DF, Lottenbach KR, Blazevic A, Turan A, Blevins TP, Pacatte TP, Yu Y, Mitchell MC, Hoft SG, Belshe RB. Comparisons of the Humoral and Cellular Immune Responses Induced by Live Attenuated Influenza Vaccine and Inactivated Influenza Vaccine in Adults. Clin Vaccine Immunol. 2017 Jan 5;24(1):e00414-16. doi: 10.1128/CVI.00414-16. Print 2017 Jan.
    Results Reference
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    Live Attenuated Influenza Vaccine (LAIV) Versus Trivalent Inactivated Influenza Vaccine in Healthy Adults 18-49 Years

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