Assess the Safety & Immunogenicity of Prime-Boost Vaccination Strategies Using H5Nx Virus Vaccine Adjuvanted With AS03 or MF59
Condition: Influenza A Virus, H5N1 Subtype
MeSH terms: Influenza, Human
Intervention: VN; IN; dk/BANG; gf/WA; bhg/QL; AS03 adjuvant; MF59 adjuvant
Intervention description: 0.5 mL vaccine (H5 vaccine antigen plus adjuvant) per dose; 0.5 mL vaccine (H5 vaccine antigen plus adjuvant) per dose; 0.5 mL vaccine (H5 vaccine antigen plus adjuvant) per dose; 0.5 mL vaccine (H5 vaccine antigen plus adjuvant) per dose; 0.5 mL vaccine (H5 vaccine antigen plus adjuvant) per dose; 0.5 mL vaccine (H5 vaccine antigen plus adjuvant) per dose; 0.5 mL vaccine (H5 vaccine antigen plus adjuvant) per dose
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 720.0
Sex: All
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: vaccine; adjuvant; Influenza in Birds; MF59; AS03

Summary:

      The main purpose of this study is to assess the ability of H5 influenza virus vaccines and
      adjuvants present in the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS) to
      generate an immune response to homologous and to antigenically distant heterologous H5
      influenza virus strains.

      The study is designed to evaluate the safety and immunogenicity of vaccination strategies
      with homologous or antigenically distant heterologous H5 influenza virus vaccines
      administered with AS03 or MF59 adjuvant.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Is a male or nonpregnant female 18 to 49 years of age, inclusive, on Day 1 (first
             vaccination).

          2. Will avoid nonstudy vaccinations until 21 days after the last vaccination.

          3. Provides written informed consent prior to the initiation of any study-related
             procedures.

          4. Has a stable health status, as established by physical examination, vital sign
             measurements, and medical history.

          5. Has access to a consistent and reliable means of telephone contact, which may be in
             the home, workplace, or by personal mobile electronic device.

          6. Is able to understand and comply with planned study procedures.

          7. Lives a reasonable distance from the site to be able to travel to and from the site
             for follow-up visits and agrees to go to the site for evaluation in the case of an
             adverse event.

          8. Agrees to stay in contact with the site for the duration of the study, has no current
             plans to move from the study area, and provides updated contact information as
             necessary.

        Exclusion Criteria:

          1. Has a known allergy to eggs or other components of the vaccine (including gelatin,
             formaldehyde, octoxinol-9, thimerosal, or chicken protein), or allergy to
             squalene-based adjuvants or has had severe reactions following previous immunizations
             with contemporary influenza virus vaccines.

          2. A woman who has a positive urine pregnancy test prior to vaccination in this study or
             a woman who is breastfeeding.

          3. A female of childbearing potential (a) who refuses to use an acceptable method of
             birth control (b) from Day 1 (first vaccination) to end-of-study visit and, if
             sexually active, who has not used a reliable birth control method for at least 2
             months prior to Day 1 (first vaccination).

               1. Female of childbearing potential is defined as post-onset menarche and
                  premenopausal female capable of becoming pregnant. This does not include females
                  who meet any of the following conditions: menopausal >1 year, tubal ligation >1
                  year, bilateral salpingo-oophorectomy, or hysterectomy.

               2. Adequate contraception is defined as a contraceptive method with failure rate of
                  less than 1% per year when used consistently and correctly and, when applicable,
                  in accordance with the product label, for example: abstinence from penile-vaginal
                  intercourse; oral contraceptives, either combined or progestogen alone;
                  injectable progestogen; implants of etonogestrel or levonorgestrel; estrogenic
                  vaginal ring; percutaneous contraceptive patches; intrauterine device or
                  intrauterine system; male partner sterilization at least 6 months prior to the
                  female Day 1 (first vaccination), and this male is the sole partner for that
                  subject (The information on the male sterility can come from the site personnel's
                  review of the subject's medical records or interview with the subject on her
                  medical history); male condom combined with a vaginal spermicide (foam, gel,
                  film, cream, or suppository); male condom combined with a female diaphragm,
                  either with or without a vaginal spermicide (foam, gel, film, cream, or
                  suppository).

          4. Is immunosuppressed as a result of an underlying illness or treatment, or anticancer
             chemotherapy or radiation therapy (cytotoxic) within the preceding 36 months prior to
             Day 1 (first vaccination).

          5. Has an active neoplastic disease or a history of any hematologic malignancy. A subject
             with superficial skin cancer who does not require intervention other than local
             excision is not excluded.

          6. Has long-term use (≥14 consecutive days) of glucocorticoids including oral or
             parenteral prednisone or equivalent (>20 mg total dose per day) or high-dose inhaled
             steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within 1 month
             prior to screening. (Low-dose [≤800 mcg/day of beclomethasone dipropionate or
             equivalent] inhaled and topical steroids are allowed).

          7. Has a diagnosis of schizophrenia, bipolar disease, or other major psychiatric
             diagnosis.

          8. Has been hospitalized for psychiatric illness, history of suicide attempt, or
             confinement for danger to self or others, within the past 10 years.

          9. Has a neurological or psychiatric diagnosis, which, although stable, is judged by the
             investigator to render the potential subject unable or unlikely to comply with the
             protocol or to provide accurate safety reports.

         10. Has received immunoglobulin or other blood product (with the exception of Rho[D]
             immune globulin) within the 3 months prior to Day 1 (first vaccination).

         11. Has received any live vaccine within 4 weeks or inactivated vaccines within 2 weeks
             prior to Day 1 (first vaccination). This includes seasonal influenza vaccines.

         12. Has an acute or chronic medical condition that, in the opinion of the investigator,
             would render vaccination unsafe or would interfere with the evaluation of responses.
             This includes potentially immune-mediated medical conditions such as Guillain-Barré
             syndrome, narcolepsy, current or history of autoimmune or chronic inflammatory
             disease.

         13. Has a first-degree relative with narcolepsy.

         14. Has an acute illness, including body temperature greater than 100.4°F, at screening,
             immediately prior to each vaccination or, per subject report, within 3 days prior to
             each vaccination. Subjects with an acute illness can be rescheduled for a vaccination
             as long as the vaccination visit is within the visit window. Note that subjects may
             return for randomization following resolution of the acute illness as long as
             recruitment remains open and subjects are within 14 days of signing consent.

         15. Has a Grade 2 or greater (by US Food and Drug Administration toxicity grade) safety
             laboratory value at screening.

         16. Has received an experimental agent (vaccine, biologic, device, blood product, or
             medication) within 1 month prior to Day 1 (first vaccination) in this study or plans
             receipt of an experimental agent during the study period.

         17. Is participating or plans to participate in another interventional clinical study
             (either active or follow-up phase) during the study period.

         18. Has received an influenza H5 vaccine in the past or has a history of H5 influenza
             infection prior to enrollment.

         19. Has known human immunodeficiency virus, hepatitis B, or hepatitis C infection.

         20. Has a history of alcohol or drug abuse within 5 years prior to Day 1 (first
             vaccination).

         21. Has a body mass index >35 kg/m2.

         22. Has any condition that would, in the opinion of the investigator, place him or her at
             an unacceptable risk of injury or render him or her unable to meet the requirements of
             the protocol (including site of injection reactogenicity assessments).

         23. Is a first-degree relative of any person working on this study: site or sponsor.