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Reactogenicity, Safety and Immunogenicity of a LAIV H7N9 Influenza Vaccine

Primary Purpose

Influenza

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
H7N9 live influenza vaccine
Placebo
Sponsored by
Research Institute of Influenza, Russia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza focused on measuring influenza vaccine pandemic

Eligibility Criteria

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

Inclusion Criteria:

  • Legal male or female adult 18 through 49 years of age at the enrollment visit.
  • Literate and willing to provide written informed consent.
  • A signed informed consent.
  • Free of obvious health problems, as established by the medical history and screening evaluations, including physical examination.
  • Capable and willing to complete diary cards and willing to return for all follow-up visits
  • Willing to comply with the rules of the isolation unit (including willing and able to take oseltamivir influenza antiviral medication, should that be recommended by a study physician).
  • For females, willing to take reliable birth control measures through day 56.

Exclusion Criteria:

  • Participation in another clinical trial involving any therapy within the previous three months or planned enrollment in such a trial during the period of this study.
  • Receipt of any non-study vaccine within four weeks prior to enrollment or refusal to postpone receipt of such vaccines until four weeks after study completion.
  • Practice of nasal irrigation on a regular basis within the past six months or has engaged in nasal irrigation within two weeks prior to enrollment.
  • Recent history of frequent nose bleeds (more than 5 within the past year).
  • Clinically relevant abnormal paranasal anatomy.
  • Recent history (within the past month) of rhino or sinus surgery, or surgery for any traumatic injury of the nose.
  • Current or recent (within two weeks of enrollment) acute respiratory illness with or without fever.
  • Other acute illness at the time of study enrollment.
  • Receipt of immune globulin or other blood products within three months prior to study enrollment or planned receipt of such products during the period of subject participation in the study.
  • Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within six months prior to study enrollment (for corticosteroids, this means prednisone or equivalent, 0.5 mg per kg per day; topical steroids are allowed, exclusive of nasal.)
  • Participation in any previous trial of any H7 or H5 containing influenza vaccine.
  • History of bronchial asthma.
  • Hypersensitivity and allergy reactions after previous administration of any vaccine.
  • History of wheezing after past receipt of any live influenza vaccine.
  • Other AE following immunization (body temperature more than 40°C, collapse, non-febrile seizures, anaphylaxis), at least possibly related to previous receipt of any vaccine (not only influenza).
  • Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein.
  • Seasonal (autumnal) hypersensitivity to the natural environment.
  • Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, metabolic, neurologic, psychiatric or renal functional abnormality, as determined by medical history, physical examination or clinical laboratory screening tests, which in the opinion of the investigator, might interfere with the study objectives. Subjects with physical examination findings or clinical laboratory screening results which would be graded 2 or higher on the AE severity grading scale will be excluded from entry into the study and will be excluded from receipt of dose two of study vaccine or placebo.
  • History of leukemia or any other blood or solid organ cancer.
  • History of thrombocytopenic purpura or known bleeding disorder.
  • History of seizures.
  • Known or suspected immunosuppressive or immunodeficient condition of any kind, including HIV infection.
  • Known chronic HBV or HCV infection.
  • Known tuberculosis infection or evidence of previous tuberculosis exposure.
  • History of chronic alcohol abuse and/or illegal drug use.
  • Claustrophobia or sociophobia.
  • Pregnancy or lactation (a negative pregnancy test will be required before administration of study vaccine or placebo for all women of childbearing potential).
  • Any condition that, in the opinion of the investigator, would increase the health risk to the subject if he/she participates in the study or would interfere with the evaluation of the study objectives.
  • Allergic, including anaphylactic, reactions to the introduction of any vaccines in the subject's medical history (not only flu vaccine).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    H7N9 LAIV

    Placebo

    Arm Description

    H7N9 live influenza vaccine

    Lyophilized purified allantoic fluid of chicken embryos with stabilizers

    Outcomes

    Primary Outcome Measures

    Immediate reactions
    Immediate reactions occurring within two hours of administration of any dose, measured as observed by study staff or reported by the subject to study staff
    Solicited adverse events
    Adverse events commonly associated with intranasal vaccination (solicited local and systemic reactions), measured as observed by study staff or reported by the subject to study staff
    Changes from baseline in laboratory findings
    Abnormal laboratory findings from blood and urine specimens
    Serious adverse events (SAEs)
    All SAEs during 56 days, as observed by study staff, reported by the subject to study staff, or noted by the subject on a diary card, including abnormal laboratory findings from blood specimens collected on Days 28 (pre-vaccination) and 56

    Secondary Outcome Measures

    Immune responses
    Immune responses was parameterized as the proportion of subjects with at least a four-fold rise after each dose from baseline or as the mean titer after each dose in any of the following: Serum hemagglutination inhibition (HAI) antibodies Serum neutralizing antibodies Serum immunoglobulin class A (IgA) or immunoglobulin class G (IgG) antibodies measured by enzyme-linked immunosorbent assay (ELISA) Secretory IgA antibodies from the nasal mucosa detected in nasal wick specimens using ELISA Secretory IgA antibodies in saliva specimens using ELISA
    Virus shedding
    Virus shedding with virus detected by real-time reverse transcriptase polymerase chain reaction rRTPCR in nasal swabs at any time point (at day of vaccination and daily during hospitalization).
    Virus stability
    Virus stability (virus detected and sequenced after inoculation into chicken eggs)

    Full Information

    First Posted
    June 16, 2015
    Last Updated
    June 19, 2015
    Sponsor
    Research Institute of Influenza, Russia
    Collaborators
    World Health Organization, Institute of Experimental Medicine, Russia
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02480101
    Brief Title
    Reactogenicity, Safety and Immunogenicity of a LAIV H7N9 Influenza Vaccine
    Official Title
    Reactogenicity, Safety and Immunogenicity of a Live Monovalent A/17/Anhui/2013/61 (H7N9) Influenza Vaccine
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    October 2014 (undefined)
    Primary Completion Date
    December 2014 (Actual)
    Study Completion Date
    April 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Research Institute of Influenza, Russia
    Collaborators
    World Health Organization, Institute of Experimental Medicine, Russia

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is a single centre phase I, double-blind placebo-controlled study to assess reactogenicity, safety and immunogenicity of a live monovalent A/17/Anhui/2013/61 (H7N9) influenza vaccine in healthy male and female adults, 18 through 49 years of age .

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Influenza
    Keywords
    influenza vaccine pandemic

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    40 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    H7N9 LAIV
    Arm Type
    Active Comparator
    Arm Description
    H7N9 live influenza vaccine
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Lyophilized purified allantoic fluid of chicken embryos with stabilizers
    Intervention Type
    Biological
    Intervention Name(s)
    H7N9 live influenza vaccine
    Other Intervention Name(s)
    LAIV H7N9
    Intervention Description
    H7N9 live influenza vaccine
    Intervention Type
    Biological
    Intervention Name(s)
    Placebo
    Intervention Description
    Lyophilized purified allantoic fluid of chicken embryos with stabilizers
    Primary Outcome Measure Information:
    Title
    Immediate reactions
    Description
    Immediate reactions occurring within two hours of administration of any dose, measured as observed by study staff or reported by the subject to study staff
    Time Frame
    2 hours
    Title
    Solicited adverse events
    Description
    Adverse events commonly associated with intranasal vaccination (solicited local and systemic reactions), measured as observed by study staff or reported by the subject to study staff
    Time Frame
    Greater than two hours after administration of any dose of study vaccine or placebo through 6 days following any dose
    Title
    Changes from baseline in laboratory findings
    Description
    Abnormal laboratory findings from blood and urine specimens
    Time Frame
    Days 3, 6 and 34
    Title
    Serious adverse events (SAEs)
    Description
    All SAEs during 56 days, as observed by study staff, reported by the subject to study staff, or noted by the subject on a diary card, including abnormal laboratory findings from blood specimens collected on Days 28 (pre-vaccination) and 56
    Time Frame
    4 weeks of receipt of any dose
    Secondary Outcome Measure Information:
    Title
    Immune responses
    Description
    Immune responses was parameterized as the proportion of subjects with at least a four-fold rise after each dose from baseline or as the mean titer after each dose in any of the following: Serum hemagglutination inhibition (HAI) antibodies Serum neutralizing antibodies Serum immunoglobulin class A (IgA) or immunoglobulin class G (IgG) antibodies measured by enzyme-linked immunosorbent assay (ELISA) Secretory IgA antibodies from the nasal mucosa detected in nasal wick specimens using ELISA Secretory IgA antibodies in saliva specimens using ELISA
    Time Frame
    Days 0, 28 and 56
    Title
    Virus shedding
    Description
    Virus shedding with virus detected by real-time reverse transcriptase polymerase chain reaction rRTPCR in nasal swabs at any time point (at day of vaccination and daily during hospitalization).
    Time Frame
    Days 0-6 after each dose
    Title
    Virus stability
    Description
    Virus stability (virus detected and sequenced after inoculation into chicken eggs)
    Time Frame
    Days 0-6 after each dose
    Other Pre-specified Outcome Measures:
    Title
    Cellular immune responses (cytokine and T-cell)
    Description
    Cellular immune responses (cytokine and T-cell) was measured using isolated peripheral blood mononuclear cells (PBMCs) tested by flow cytometry and/or enzyme-linked immunosorbent spot (ELISPOT) assay.
    Time Frame
    Days 0, 28 and 56

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    49 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Legal male or female adult 18 through 49 years of age at the enrollment visit. Literate and willing to provide written informed consent. A signed informed consent. Free of obvious health problems, as established by the medical history and screening evaluations, including physical examination. Capable and willing to complete diary cards and willing to return for all follow-up visits Willing to comply with the rules of the isolation unit (including willing and able to take oseltamivir influenza antiviral medication, should that be recommended by a study physician). For females, willing to take reliable birth control measures through day 56. Exclusion Criteria: Participation in another clinical trial involving any therapy within the previous three months or planned enrollment in such a trial during the period of this study. Receipt of any non-study vaccine within four weeks prior to enrollment or refusal to postpone receipt of such vaccines until four weeks after study completion. Practice of nasal irrigation on a regular basis within the past six months or has engaged in nasal irrigation within two weeks prior to enrollment. Recent history of frequent nose bleeds (more than 5 within the past year). Clinically relevant abnormal paranasal anatomy. Recent history (within the past month) of rhino or sinus surgery, or surgery for any traumatic injury of the nose. Current or recent (within two weeks of enrollment) acute respiratory illness with or without fever. Other acute illness at the time of study enrollment. Receipt of immune globulin or other blood products within three months prior to study enrollment or planned receipt of such products during the period of subject participation in the study. Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within six months prior to study enrollment (for corticosteroids, this means prednisone or equivalent, 0.5 mg per kg per day; topical steroids are allowed, exclusive of nasal.) Participation in any previous trial of any H7 or H5 containing influenza vaccine. History of bronchial asthma. Hypersensitivity and allergy reactions after previous administration of any vaccine. History of wheezing after past receipt of any live influenza vaccine. Other AE following immunization (body temperature more than 40°C, collapse, non-febrile seizures, anaphylaxis), at least possibly related to previous receipt of any vaccine (not only influenza). Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein. Seasonal (autumnal) hypersensitivity to the natural environment. Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, metabolic, neurologic, psychiatric or renal functional abnormality, as determined by medical history, physical examination or clinical laboratory screening tests, which in the opinion of the investigator, might interfere with the study objectives. Subjects with physical examination findings or clinical laboratory screening results which would be graded 2 or higher on the AE severity grading scale will be excluded from entry into the study and will be excluded from receipt of dose two of study vaccine or placebo. History of leukemia or any other blood or solid organ cancer. History of thrombocytopenic purpura or known bleeding disorder. History of seizures. Known or suspected immunosuppressive or immunodeficient condition of any kind, including HIV infection. Known chronic HBV or HCV infection. Known tuberculosis infection or evidence of previous tuberculosis exposure. History of chronic alcohol abuse and/or illegal drug use. Claustrophobia or sociophobia. Pregnancy or lactation (a negative pregnancy test will be required before administration of study vaccine or placebo for all women of childbearing potential). Any condition that, in the opinion of the investigator, would increase the health risk to the subject if he/she participates in the study or would interfere with the evaluation of the study objectives. Allergic, including anaphylactic, reactions to the introduction of any vaccines in the subject's medical history (not only flu vaccine).
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Larisa G Rudenko, MD PhD DSc
    Organizational Affiliation
    Institute of Experimental Medicine
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    26673391
    Citation
    Rudenko L, Isakova-Sivak I, Naykhin A, Kiseleva I, Stukova M, Erofeeva M, Korenkov D, Matyushenko V, Sparrow E, Kieny MP. H7N9 live attenuated influenza vaccine in healthy adults: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Infect Dis. 2016 Mar;16(3):303-10. doi: 10.1016/S1473-3099(15)00378-3. Epub 2015 Dec 8.
    Results Reference
    derived

    Learn more about this trial

    Reactogenicity, Safety and Immunogenicity of a LAIV H7N9 Influenza Vaccine

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