Sanofi 2017 H7N9 With/Without AS03 in Adults/Elderly
Condition: Avian Influenza; Influenza Immunisation
MeSH terms: Influenza, Human; Influenza in Birds
Intervention: AS03; Inactivated influenza H7N9 vaccine; Phosphate Buffered Saline (PBS) diluent
Intervention description: Oil-in-water emulsion based adjuvant system.; Monovalent 2017 H7N9 inactivated influenza vaccine; Diluent for 2017 Monovalent Inactivated Influenza A/H7N9 virus vaccine (2017 H7N9 IIV)
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 720.0
Sex: All
Minimum age: 19 Years
Maximum age: 99 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: A/H7N9; Immunogenicity; Influenza; Safety; Sanofi Pasteur; Vaccine

Summary:

      This is a randomized, double-blinded, Phase II study in healthy males and non-pregnant
      females 19 years and older that is designed to assess the safety, reactogenicity, and
      immunogenicity of a pre-pandemic 2017 monovalent inactivated influenza A/H7N9 virus vaccine
      (2017 H7N9 IIV) administered at different dosages given with AS03 adjuvant and phosphate
      buffered saline (PBS) diluent, with AS03 adjuvant only, and without adjuvant. Eligible
      subjects will be randomized into 5 study groups, stratified by age. The study will enroll up
      to 420 individuals 19-64 years old and up to 300 individuals who are 65 years old and older.
      Study duration is approximately 16 months with subject participation duration approximately
      13 months. The primary objectives of this study are: 1) to assess the safety and
      reactogenicity following receipt of two doses of 2017 H7N9 IIV administered intramuscularly
      at different dosages approximately 21 days apart given with or without AS03 adjuvant; 2) to
      assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses
      following receipt of two doses of 2017 H7N9 IIV administered intramuscularly at different
      dosages approximately 21 days apart with or without AS03 adjuvant, stratified by age of
      recipient.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provide written informed consent prior to initiation of any study procedures.

          2. Are able to understand and comply with planned study procedures and be available for
             all study visits.

          3. Are males or non-pregnant females, 19 years of age and older, inclusive.

          4. Are in good health*. *As determined by medical history and physical examination to
             evaluate acute or currently ongoing chronic medical diagnoses or conditions, defined
             as those that have been present for at least 90 days, which would affect the
             assessment of the safety of subjects or the immunogenicity of study vaccinations.
             Chronic medical diagnoses or conditions should be stable for the last 60 days (no
             hospitalizations, ER, or urgent care for condition and no adverse symptoms that need
             medical intervention such as medication change/supplemental oxygen). This includes no
             change in chronic prescription medication, dose, or frequency as a result of
             deterioration of the chronic medical diagnosis or condition in the 60 days prior to
             enrollment. Any prescription change that is due to change of health care provider,
             insurance company, etc., or that is done for financial reasons, as long as in the same
             class of medication, will not be considered a deviation of this inclusion criterion.
             Any change in prescription medication due to improvement of a disease outcome, as
             determined by the site principal investigator or appropriate sub-investigator, will
             not be considered a deviation of this inclusion criterion. Subjects may be on chronic
             or as needed (prn) medications if, in the opinion of the site principal investigator
             or appropriate sub-investigator, they pose no additional risk to subject safety or
             assessment of reactogenicity and immunogenicity and do not indicate a worsening of
             medical diagnosis or condition. Similarly, medication changes subsequent to enrollment
             and study vaccination are acceptable provided there was no deterioration in the
             subject's chronic medical condition that necessitated a medication change, and there
             is no additional risk to the subject or interference with the evaluation of responses
             to study vaccination. Note: Topical, nasal, and inhaled medications (with the
             exception of inhaled corticosteroids as outlined in the Subject Exclusion Criteria),
             herbals, vitamins, and supplements are permitted.

          5. Oral temperature is less than 100.0 degrees Fahrenheit.

          6. Pulse is 47 to 100 bpm, inclusive.

          7. Systolic blood pressure is 85 to 150 mmHg, inclusive (subjects <65 years of age), 85
             to 160 mmHg, inclusive (subjects = / > 65 years of age).

          8. Diastolic blood pressure is 55 to 95 mmHg, inclusive.

          9. Erythrocyte sedimentation rate (ESR) is less than 30 mm per hour.

         10. Women of childbearing potential* must use an acceptable contraception method** from 30
             days before first study vaccination until 60 days after last study vaccination.

             *Not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy,
             hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal
             sterilization) with documented radiological confirmation test at least 90 days after
             the procedure, and still menstruating or <1 year of the last menses if menopausal.

             **Acceptable contraception includes non-male sexual relationships, abstinence from
             sexual intercourse with a male partner, monogamous relationship with vasectomized
             partner who has been vasectomized for 180 days or more prior to the subject receiving
             the first study vaccination, barrier methods such as condoms or diaphragms with
             spermicide or foam, effective intrauterine devices, NuvaRing(R), and licensed hormonal
             methods such as implants, injectables, or oral contraceptives ("the pill").

         11. Women of childbearing potential must have a negative urine or serum pregnancy test
             within 24 hours prior to study vaccination.

        Exclusion Criteria:

          1. Have an acute illness*, as determined by the site principal investigator or
             appropriate sub-investigator, within 72 hours prior to study vaccination.

             *An acute illness which is nearly resolved with only minor residual symptoms remaining
             is allowable if, in the opinion of the site principal investigator or appropriate
             sub-investigator, the residual symptoms will not interfere with the ability to assess
             safety parameters as required by the protocol.

          2. Have any medical disease or condition that, in the opinion of the site principal
             investigator or appropriate sub-investigator, is a contraindication to study
             participation*.

             *Including acute or chronic medical disease or condition, defined as persisting for at
             least 90 days, that would place the subject at an unacceptable risk of injury, render
             the subject unable to meet the requirements of the protocol, or may interfere with the
             evaluation of responses or the subject's successful completion of this trial.

          3. Have immunosuppression as a result of an underlying illness or treatment, a recent
             history or current use of immunosuppressive or immunomodulating disease therapy.

          4. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior
             to study vaccination.

          5. Have known active neoplastic disease or a history of any hematologic malignancy.
             Non-melanoma, treated, skin cancers are permitted.

          6. Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.

          7. Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based
             adjuvants, or other components of the study vaccine.

          8. Have a history of severe reactions following previous immunization with licensed or
             unlicensed influenza vaccines.

          9. Have a personal or family history of narcolepsy.

         10. Have a history of Guillain-Barré syndrome.

         11. Have a history of convulsions or encephalomyelitis within 90 days prior to study
             vaccination.

         12. Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).

         13. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.

         14. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other
             psychiatric diagnosis that may interfere with subject compliance or safety
             evaluations.

         15. 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.

         16. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose
             within 30 days prior to study vaccination.

         17. Have taken high-dose inhaled corticosteroids* within 30 days prior to each study
             vaccination.

             *High-dose defined as per age as using inhaled high dose per reference chart
             https://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/quick-refere
             nce-html#estimated-comparative-daily-doses

         18. Received a licensed live vaccine within 30 days prior to the first study vaccination,
             or plan to receive a licensed live vaccine within 30 days before or after each study
             vaccination.

         19. Received or plan to receive a licensed, inactivated, vaccine (excluding all flu
             vaccines) within 14 days before or after each study vaccination.

         20. Received or plan to receive an inactivated seasonal flu vaccine within 21 days before
             or after each study vaccination.

         21. Received immunoglobulin or other blood products (with exception of Rho D
             immunoglobulin) within 90 days prior to each study vaccination.

         22. Received an experimental agent* within 30 days prior to the first study vaccination,
             or expect to receive an experimental agent** during the 13-month trial-reporting
             period.

             *Including vaccine, drug, biologic, device, blood product, or medication.

             **Other than from participation in this trial.

         23. Are participating or plan to participate in another clinical trial with an
             interventional agent* that will be received during the 13-month trial-reporting
             period.

             *Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or
             medication.

         24. Received or plan to receive an influenza A/H7 vaccine* or have a history of influenza
             A/H7 subtype infection.

             *And assigned to a group receiving influenza A/H7 vaccine, does not apply to
             documented placebo recipients.

         25. Have traveled to mainland China and had substantial* direct contact with live or
             freshly slaughtered poultry or pigeons within the past five years.

             *Substantial contact is defined as visited a poultry farm and/or a live poultry
             market.

         26. Occupational exposure to or substantial direct physical contact* with birds in the
             past year and through the 21 days after the second study vaccination.

             *Exposure to free range chickens in the yard is exclusionary. Casual contact with
             birds at petting zoos or county or state fairs or having pet birds does not exclude
             subjects from study participation.

         27. Female subjects who are breastfeeding or plan to breastfeed at any given time from the
             first study vaccination until 30 days after the last study vaccination.

         28. Plan to travel outside the US (continental US, Hawaii, and Alaska) from enrollment
             through 21 days after the second study vaccination.