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Safety Trial of Live Attenuated Influenza (H7N3) Vaccine

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: NCT01511419
Recruitment Status : Completed
First Posted : January 18, 2012
Results First Posted : April 22, 2019
Last Update Posted : April 22, 2019
Sponsor:
Collaborators:
Ministry of Health, Russian Federation
Research Institute of Influenza, Russia
Institute of Experimental Medicine, Russia
Information provided by (Responsible Party):
PATH

Brief Summary:
The study hypothesis is that two doses of cold-adapted, live monovalent A/17/mallard/Netherlands/00/95 (H7N3) influenza vaccine will be safe and immunogenic in healthy adults.

Condition or disease Intervention/treatment Phase
Influenza Avian Influenza Biological: LAIV H7N3 Biological: placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Reactogenicity, Safety and Immunogenicity of a Live Monovalent A/17/Mallard/Netherlands/00/95 (H7N3) Influenza Vaccine
Study Start Date : April 2012
Actual Primary Completion Date : June 2012
Actual Study Completion Date : July 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: LAIV H7N3

Test drug/agent: Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine (LAIV H7N3) grown in embryonated chicken eggs.

Name of active ingredient(s): Live-attenuated A/17/mallard/Netherlands/00/95 influenza vaccine.

Dose: ≥7.5 log egg infectious dose (EID) 50/0.5 ml dose; 0.25 ml/nare.

Route of administration: Intranasal aerosol.

Duration of treatment: Two doses were delivered, one on Day 0 and one on Day 28.

Biological: LAIV H7N3
2 doses of vaccine
Other Name: A/17/mallard/Netherlands/00/95 (H7N3)

Placebo Comparator: Placebo

Reference drug: Placebo; saline inoculated in embryonated chicken eggs and subsequently prepared in the same way as test vaccine.

Dose: 0.5 ml; 0.25 ml/nare

Route of administration: Intranasal aerosol

Duration of treatment: Two doses were delivered, one on Day 0 and one on Day 28

Biological: placebo
2 doses of placebo




Primary Outcome Measures :
  1. Number of Participants With Immediate Reactions [ Time Frame: 2 hours post-administration on Days 0 and 28 ]
    From administration of any dose, immediate reaction measured as observed by study staff or reported by the subject to study staff in case of an anaphylactic reaction.

  2. Adverse Events Associated With Intranasal Vaccination [ Time Frame: Greater than 2 hours through 7 days following any dose ]
    From solicited local and systemic reactions

  3. All Other Adverse Events [ Time Frame: 7 days following any dose ]
    Including unsolicited events and abnormal laboratory findings

  4. Participants With Serious Adverse Events (SAEs) [ Time Frame: Within 4 weeks of receipt of any dose ]
    Including abnormal laboratory findings


Secondary Outcome Measures :
  1. Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) [ Time Frame: 28 days (Dose 1) and 56 days (Dose 2) ]
    Seroconversion was defined as at least a four-fold rise after each dose from baseline or as the mean titer after each dose

  2. Number/Percentage of Subjects With Serum Neutralizing Antibodies [ Time Frame: 28 days (Dose 1) and 56 days (Dose 2) ]
    Measured using microneutralization assay. Seroconversion was defined as at least a four-fold rise after each dose from baseline or as the mean titer after each dose

  3. Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) [ Time Frame: 28 days (Dose 1) and 56 days (Dose 2) ]
    Measured by enzyme-linked immunoassay (EIA). Seroconversion was defined as at least a four-fold rise after each dose from baseline or as the mean titer after each dose

  4. Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) [ Time Frame: 28 days (Dose 1) and 56 days (Dose 2) ]
    Measured by enzyme-linked immunoassay (EIA). Seroconversion was defined as at least a four-fold rise after each dose from baseline or as the mean titer after each dose

  5. Number/Percentage of Subjects With Seroconversion for Mucosal IgA [ Time Frame: 28 days (Dose 1) and 56 days (Dose 2) ]
    From nasal wick specimen. Seroconversion was defined as at least a four-fold rise after each dose from baseline or as the mean titer after each dose

  6. Geometric Mean Titers (GMTs) for Serum Hemagglutination Inhibition (HAI) Antibodies (4 Haemagglutinating Units of H7N3) [ Time Frame: 0 days, 28 days (Dose 1) and 56 days (Dose 2) ]
    HAI test was performed by standard procedure with human red blood cells utilizing either 4 haemagglutinating units (HAU) of H7N3.

  7. Geometric Mean Titers (GMTs) for Serum Hemagglutination Inhibition (HAI) Antibodies (2 Haemagglutinating Units of H7N3) [ Time Frame: 0 days, 28 days (Dose 1) and 56 days (Dose 2) ]
    HAI test was performed by standard procedure with human red blood cells utilizing 2 haemagglutinating units (HAU) of H7N3.

  8. Geometric Mean Titers (GMTs) for Serum Neutralizing Antibodies [ Time Frame: 0 days, 28 days (Dose 1) and 56 days (Dose 2) ]
    Measured by microneutralization assay

  9. Number/Percentage of Vaccinated Subjects Shedding Virus After First Dose [ Time Frame: Days 1, 2, 3 & 4 ]
    Detected by real-time reverse transcriptase polymerase chain reaction (rRTPCR) in nasal swabs or conjunctival swabs or by isolation in chicken embryos.

  10. Number/Percentage of Subjects Shedding Virus After Second Dose [ Time Frame: Day 29, 30, 31 and 32 ]
    Detected by real-time reverse transcriptase polymerase chain reaction (rRTPCR) in nasal swabs or conjunctival swabs or by isolation in chicken embryos.


Other Outcome Measures:
  1. Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses [ Time Frame: Days 0, 28 & 56 ]

    H7N3-specific T cell responses were examined in peripheral blood mononuclear cells (PBMCs) obtained from all the study subjects before vaccination (Day 0), 28 days after the first vaccination (Day 28) and 28 days after revaccination (Day 56). To calculate the frequency of virus-specific T cells we quantified all cells positive for IFNγ after in vitro stimulation with whole H7N3 virion.

    Increases in the antigen-specific CD4+T-cell levels exceeding 3 standard deviations from the levels in the mean of the placebo were considered positive responses.


  2. Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses [ Time Frame: Days 0, 28 & 56 ]

    H7N3-specific T cell responses were examined in PBMCs obtained from all the study subjects before vaccination (Day 0), 28 days after the first vaccination (Day 28) and 28 days after revaccination (Day 56). To calculate the frequency of virus-specific T cells we quantified all cells positive for IFNγ after in vitro stimulation with whole H7N3 virion.

    Increases in the antigen-specific CD4+T-cell levels exceeding 3 standard deviations from the levels in the mean of the placebo were considered positive responses.


  3. Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses [ Time Frame: Days 0, 28 & 56 ]

    H7N3-specific T cell responses were examined in PBMCs obtained from all the study subjects before vaccination (Day 0), 28 days after the first vaccination (Day 28) and 28 days after revaccination (Day 56). To calculate the frequency of virus-specific T cells we quantified all cells positive for IFNγ after in vitro stimulation with whole H7N3 virion.

    Increases in the antigen-specific CD4+T-cell levels exceeding 3 standard deviations from the levels in the mean of the placebo were considered positive responses.


  4. Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses [ Time Frame: Days 0, 28 & 56 ]

    H7N3-specific T cell responses were examined in PBMCs obtained from all the study subjects before vaccination (Day 0), 28 days after the first vaccination (Day 28) and 28 days after revaccination (Day 56). To calculate the frequency of virus-specific T cells we quantified all cells positive for IFNγ after in vitro stimulation with whole H7N3 virion.

    Increases in the antigen-specific CD4+T-cell levels exceeding 3 standard deviations from the levels in the mean of the placebo were considered positive responses.


  5. Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses [ Time Frame: Days 0, 28 & 56 ]

    H7N3-specific T cell responses were examined in PBMCs obtained from all the study subjects before vaccination (Day 0), 28 days after the first vaccination (Day 28) and 28 days after revaccination (Day 56). To calculate the frequency of virus-specific T cells we quantified all cells positive for IFNγ after in vitro stimulation with whole H7N3 virion.

    Increases in the antigen-specific CD4+T-cell levels exceeding 3 standard deviations from the levels in the mean of the placebo were considered positive responses.


  6. Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses [ Time Frame: Days 0, 28 & 56 ]

    H7N3-specific T cell responses were examined in PBMCs obtained from all the study subjects before vaccination (Day 0), 28 days after the first vaccination (Day 28) and 28 days after revaccination (Day 56). To calculate the frequency of virus-specific T cells we quantified all cells positive for IFNγ after in vitro stimulation with whole H7N3 virion.

    Increases in the antigen-specific CD4+T-cell levels exceeding 3 standard deviations from the levels in the mean of the placebo were considered positive responses.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
  • 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 throughout the entire period of participation in the study.

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 (>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 H5 or H7 containing influenza vaccine.
  • History of asthma.
  • Hypersensitivity after previous administration of any influenza vaccine.
  • History of wheezing after past receipt of any live influenza vaccine.
  • Other AE following immunization, at least possibly related to previous receipt of any influenza vaccine.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01511419


Locations
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Russian Federation
Research Institute of Influenza
St Petersburg, Russian Federation, 197376
Sponsors and Collaborators
PATH
Ministry of Health, Russian Federation
Research Institute of Influenza, Russia
Institute of Experimental Medicine, Russia
Investigators
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Principal Investigator: Oleg I Kiselev, MD, PhD, DSc Research Institute of Influenza
Study Director: Larisa G Rudenko, MD, PhD, DSc Institute of Experimental Medicine
Study Director: Kathleen M Neuzil, MD, MPH PATH Vaccine Solutions
Study Director: Igor Victorevich Microgen Scientific Industrial Company for Immunobiological Medicines

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT01511419    
Other Study ID Numbers: LAIV-H7N3-01
First Posted: January 18, 2012    Key Record Dates
Results First Posted: April 22, 2019
Last Update Posted: April 22, 2019
Last Verified: January 2019
Keywords provided by PATH:
Influenza
Vaccine
Pandemic
H7N3
Additional relevant MeSH terms:
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Influenza, Human
Influenza in Birds
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs