2017 A/H7N9 IIV Revaccination
Condition: Avian Influenza; Influenza Immunisation
MeSH terms: Influenza, Human; Influenza in Birds
Intervention: A/H7N9; AS03; Phosphate Buffered Saline (PBS) diluent
Intervention description: Monovalent split 2017 A/H7N9 Inactivated Influenza Virus Vaccine containing the Hemagglutinin (HA) and Neuraminidase (NA) from low pathogenic avian influenza A/Hong Kong/125/2017 (H7N9) and the PB2, PB1, PA, NP, M and NS from A/Puerto Rico/8/1934 (H1N1). The HA content of the 2017 A/H7N9 vaccine formulations were determined by Single Radial Immunodiffusion (SRID) assay to be approximately two times higher (14.45 mcg of HA per 0.5 mL dose) than the targeted HA content on the label (7.5 mcg of HA per 0.5 mL dose).; AS03 oil-in-water emulsion-based adjuvant system containing DL-alpha-tocopherol, squalene, polysorbate 80, and a buffer.; 0.006M PBS diluent for Influenza Virus Vaccine.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 304.0
Sex: All
Minimum age: 19 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: A/H7N9 Inactivated Influenza Vaccine; AS03 Adjuvant; Immunogenicity; Influenza; Phase II; Reactogenicity; Safety; Vaccine

Summary:

      This is a Phase II clinical trial in up to 420 males and non-pregnant females, 19 to 70 years
      of age, inclusive, who are in good health and meet all eligibility criteria. This clinical
      trial is designed to assess the safety, reactogenicity and immunogenicity of one dose of a
      monovalent inactivated split influenza 2017 A/H7N9 virus vaccine (2017 A/H7N9 IIV),
      administered intramuscularly (IM) at 3.75 mcg hemagglutinin (HA) per dose, given with or
      without AS03 adjuvant to subjects primed with a monovalent inactivated split influenza 2013
      A/H7N9 virus vaccine (2013 A/H7N9 IIV) in DMID Protocols 13-0032 and 13-0033, or to those who
      are A/H7 IIV-naïve. Phosphate buffered saline (PBS) diluent will be used to achieve the
      targeted dosage. The study will be conducted at 9 Vaccine and Treatment Evaluation Unit
      (VTEU) sites (including their subcontractors). Study duration is approximately 17 months with
      subject participation duration up to 13 months. The primary objectives are: 1) to assess the
      safety and reactogenicity of 2017 A/H7N9 IIV given with or without AS03 adjuvant following
      receipt of one dose of study vaccine; 2) to assess the serum hemagglutination inhibition
      (HAI) and neutralizing (Neut) antibody responses following receipt of the study vaccine.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects eligible to participate in this trial must meet all of the following 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. Must agree to the collection of venous blood per protocol.

          4. Must agree to have residual specimens and samples/specimens collected during this
             trial specifically for the purpose of future research stored for future research use.

          5. Are males or non-pregnant females, 19 to 70 years of age, inclusive.

          6. 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, emergency room 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 PI 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 PI 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 (except inhaled corticosteroids as
             outlined in the Subject Exclusion Criteria as well as herbals, vitamins and
             supplements are permitted.

          7. Oral temperature is less than 100.0 degrees Fahrenheit.

          8. Pulse is 47 to 100 beats per minute, inclusive.

          9. Systolic blood pressure is 85 to 150 mmHg, inclusive.

         10. Diastolic blood pressure is 55 to 95 mmHg, inclusive.

         11. Erythrocyte Sedimentation Rate (ESR) is less than 30 mm per hour.

         12. Women of childbearing potential** must use an acceptable contraception method*** from
             30 days before study vaccination until 60 days after 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 has passed since the last menses if
             menopausal.

             ***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 study
             vaccination, barrier methods such as condoms or diaphragms/cervical cap with
             spermicide, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods
             such as implants, injectables or oral contraceptives ("the pill").

         13. Women of childbearing potential must have a negative urine or serum pregnancy test
             within 24 hours prior to study vaccination.

         14. Received 1 or 2 doses of 2013 A/H7N9 IIV with or without AS03 or MF59 adjuvant in DMID
             Protocols 13-0032 or 13-0033, or are A/H7 IIV-naïve.

        Exclusion Criteria:

        Subjects eligible to participate in this trial must not meet any of the following exclusion
        criteria:

          1. Have an acute illness*, as determined by the site PI 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 PI 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 PI 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 cytotoxic anticancer chemotherapy or radiation therapy 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 (GBS).

         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.

             ***As determined by the site PI or appropriate sub-investigator.

         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 study
             vaccination.

             ****High-dose defined as per age as using inhaled high-dose per reference chart in the
             National Heart, Lung and Blood Institute Guidelines for the Diagnosis and Management
             of Asthma (EPR-3) or other lists published in UPTODATE.

         18. Received or plan to receive a licensed, live vaccine within 30 days before or after
             study vaccination.

         19. Received or plan to receive a licensed, inactivated vaccine (excluding all licensed,
             seasonal IIVs) within 14 days before or after study vaccination.

         20. Received or plan to receive a licensed, seasonal IIV within 21 days before or after
             study vaccination.

         21. Received immunoglobulin or other blood products (except Rho D immunoglobulin) within
             90 days prior to study vaccination.

         22. Received an experimental agent***** within 30 days prior to study vaccination or
             expect to receive an experimental agent****** during the trial-reporting
             period*******.

             *****Including vaccine, drug, biologic, device, blood product, or medication.

             ******Other than from participation in this trial.

             *******Approximately 12 months after study vaccination.

         23. Are participating or plan to participate in another clinical trial with an
             interventional agent******** that will be received during the trial-reporting
             period*********.

             ********Including licensed or unlicensed vaccine, drug, biologic, device, blood
             product, or medication.

             *********Approximately 12 months after study vaccination.

         24. Have a history of influenza A/H7 subtype infection.

         25. Had substantial direct contact********** with live or freshly slaughtered poultry or
             pigeons while in mainland China within the past five years.

             **********Substantial direct 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 21 days after 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.

         28. Plan to travel outside the US (continental US, Hawaii and Alaska) from the time of
             study vaccination through 21 days after study vaccination.