Safety and Immunogenicity of a Live-attenuated Universal Flu Vaccine Followed by an Inactivated Universal Flu Vaccine
Condition: Influenza; Vaccine
MeSH terms: Influenza, Human
Intervention: cH8/1N1 LAIV; AS03-adjuvanted cH5/1N1 IIV; cH5/1N1 IIV; AS03-adjuvanted cH8/1N1 IIV; Normal saline; Phosphate buffered saline (PBS)
Intervention description: Live-attenuated influenza virus vaccine (LAIV) expressing chimeric hemagglutinin (HA) with the H8 head and H1 stalk and neuraminidase (NA) subtype 1 (N1) (cH8/1N1):
HA head, A/mallard/Sweden/24/2002 (H8N4); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1) containing the backbone of the cold-adapted/temperature sensitive of the Russian LAIV A/Leningrad/134/17/1957 (Len17 IDCDCRG46D).
Administered intranasally as drops at a dose of 10⁷·⁵ (plus or minus ⁰·⁵) 50% egg infectious dose (EID50), formulated in a total volume of 0.5 mL sterile saline (0.25 mL per nostril).; Chimeric H5 head with H1 stalk plus N1 (cH5/1N1) split virion inactivated influenza virus vaccine (IIV) plus AS03 adjuvant: HA head, A/Vietnam/1203/2004 (H5N1); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1).
Administered intramuscularly at a dose of 15 μg of hemagglutinin in a volume of 0.5 mL of phosphate buffered saline (PBS).; Chimeric H5 head with H1 stalk plus N1 (cH5/1N1) split virion inactivated influenza virus vaccine (IIV):
HA head, A/Vietnam/1203/2004 (H5N1); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1).
Administered intramuscularly at a dose of 15 μg of hemagglutinin in a volume of 0.5 mL of phosphate buffered saline (PBS).; Chimeric H8 head with H1 stalk plus N1 (cH8/1N1) inactivated influenza vaccine plus AS03 adjuvant: HA head, A/mallard/Sweden/24/2002 (H8N4); HA stalk, A/California/04/2009 (H1N1); NA, A/California/04/2009 (H1N1).
Administered intramuscularly at a dose of 15 μg of hemagglutinin in a volume of 0.5 mL of phosphate buffered saline (PBS).; Administered intranasally as 0.25 mL nasal drops per nostril; Administered intramuscularly as 0.5 mL injection
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Eligible enrolled subjects will be randomized to any of the treatment arms (LAIV-IIV, Groups 1, 2, and 3; or IIV-IIV, Groups 4 and 5) under one allocation sequence, stratified by site, to allow comparability between study groups, such as LAIV-IIV vs IIV-IIV regimens (Groups 1 vs 4). Groups 1-3 will be inpatient and receive either LAIV or placebo as nasal drops at Dose 1. Groups 4-5 ill be outpatient and receive either IIV or placebo as an injection at Dose 1.
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: An unblinded pharmacist will prepare Dose 1 and Dose 2. Participants and study staff will remain blinded to their exact treatment group but will be unblinded to their overall group allocation (inpatient or outpatient).
Enrollment: 65.0
Sex: All
Minimum age: 18 Years
Maximum age: 39 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: live attenuated influenza vaccine; inactivated influenza vaccine

Summary:

      The clinical study will evaluate safety and the immune response of a prime- boost regimen
      with a live attenuated influenza vaccine (LAIV) prime and an inactivated split influenza
      vaccine (IIV) boost with or without adjuvant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able to understand planned study procedures and demonstrate comprehension of the
             protocol procedures and knowledge of study by passing a written examination prior to
             vaccination.

          -  In the opinion of the investigator, can and will comply with the requirements of the
             protocol (e.g., completion of the diary cards, return for follow-up visits).

          -  Written informed consent obtained from the subject prior to performance of any study
             specific procedure.

          -  Male or non-pregnant female between, and including, 18 and 39 years of age at the time
             of the first vaccination.

          -  Healthy subjects without acute or chronic, clinically significant pulmonary,
             cardiovascular, hepatic or renal functional abnormality*.

          -  Female subjects of non-childbearing potential may be enrolled in the study.

          -  Female subjects of childbearing potential must have a negative pregnancy test within
             24 hours of vaccination.

          -  Female subjects of childbearing potential must have practiced adequate contraception
             for 30 days prior to first vaccination and agree to continue adequate contraception
             until 2 months after completion of the vaccination series (Month 5).

          -  Male subjects must be surgically sterile (e.g., vasectomy) or agree to practice
             adequate contraception from the first vaccination until 2 months after completion of
             the vaccination series (Month 5). Please refer to the glossary of terms for the
             definition of adequate contraception.

        Exclusion Criteria:

          -  Use of any investigational or non-registered product (drug or vaccine) other than the
             study vaccines.

          -  Any medical condition that in the judgment of the investigator would make
             intramuscular injection unsafe.

          -  Medically diagnosed deviated nasal septum or nasal obstruction.

          -  Chronic administration (defined as more than 14 days in total) of immunosuppressants
             or other immune-modifying drugs within 6 months before the first dose.

          -  Administration of long-acting immune-modifying drugs (e.g., infliximab, rituximab)
             within 6 months before the first dose (Visit 03), or planned administration any time
             during the study period.

          -  Planned administration/administration of a vaccine not foreseen by the study protocol
             in the period starting 30 days before the first dose (Visit 03) up to Month 15 (Visit
             15)

          -  Persons who should be annually vaccinated against influenza who live with or care for
             persons at high risk for influenza-related complications.

          -  History of influenza vaccination within 6 months prior to study enrollment or
             unwillingness to forego seasonal influenza vaccination during the entire study period.

          -  History of vaccination with an investigational pandemic influenza vaccine other than
             an 2009 H1N1 Pandemic (H1N1pdm09) vaccine.

          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, based on
             medical history and physical examination.

          -  Infection with human immunodeficiency virus regardless of clinical stage of
             immunodeficiency.

          -  History of current infection with hepatitis B virus or hepatitis C virus regardless of
             clinical presentation.

          -  History of or current autoimmune disease.

          -  Subjects diagnosed with excessive daytime sleepiness or narcolepsy; or history of
             narcolepsy in a subject's parent or sibling.

          -  History of Guillain-Barré syndrome.

          -  History of any reaction or hypersensitivity likely to be exacerbated by any component
             of the vaccines (including egg proteins); a history of anaphylactic-type reaction to
             consumption of eggs; or a history of severe adverse reaction to a previous influenza
             vaccine.

          -  Hypersensitivity to latex.

          -  Administration of immunoglobulins and/or any blood products during the period starting
             3 months before the first dose of study vaccines or planned administration during the
             study period.

          -  Pregnant or lactating female.

          -  Female planning to become pregnant or male planning to father a child or either
             planning to discontinue contraceptive precautions.

          -  Current smoker.

          -  During screening, have a positive test for opiates without a prescription.

          -  History of chronic alcohol consumption and/or drug abuse as deemed by the investigator
             to render the potential subject unable/unlikely to provide accurate safety reports.

          -  Have a history of convulsions or encephalomyelitis within 90 days prior to study
             vaccination.

          -  Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other
             psychiatric diagnosis that may interfere with subject compliance or safety
             evaluations.

          -  Have been hospitalized for psychiatric illness, history of suicide attempt, or
             confinement for danger to self or others within 10 years prior to study vaccination.

          -  Blood donation or planned blood donation within 30 days prior to the study vaccination
             through 30 days after the last blood drawn for this study.

          -  Have signs or symptoms that could confound or confuse assessment of study vaccine
             reactogenicity.

          -  Any hematological or biochemical parameter that is out of range of normal, and is
             considered clinically significant by the investigator.