H7N9 Mix and Match With AS03 and MF59 in Healthy Adults
H7N9 Mix and Match With AS03 and MF59 in Healthy Adults
This Phase II randomized, double-blinded, controlled study in up to 1000 males and
 non-pregnant females, 19 to 64 years old, inclusive, who are in good health and meet all
 eligibility criteria is designed to provide data on an A/H7N9 vaccine made with HA antigen
 derived from the influenza A/Shanghai/2/2013 virus.
This Phase II randomized, double-blinded, controlled study in up to 1000 males and
 non-pregnant females, 19 to 64 years old, inclusive, who are in good health and meet all
 eligibility criteria is designed to provide data on an A/H7N9 vaccine made with HA antigen
 derived from the influenza A/Shanghai/2/2013 virus. The study aims to address several
 critical questions, including the safety, reactogenicity, and immunogenicity of a monovalent
 influenza A/H7N9 virus vaccine manufactured by Sanofi Pasteur: 1) two doses administered at
 different dosages (3.75, 7.5, or 15 mcg of HA/0.5 mL dose) given with AS03 adjuvant
 manufactured by GlaxoSmithKline Biologicals or without adjuvant (15 mcg of HA/0.5 mL dose and
 45 mcg of HA/0.75 mL dose); and 2) a combination of two doses of the A/H7N9 vaccine (15 mcg
 of HA/0.5 mL dose) each administered with a different adjuvant (AS03 or MF59 manufactured by
 Novartis Vaccines and Diagnostics); and 3) two doses administered at 15 mcg of HA/0.5 mL dose
 given with MF59 adjuvant manufactured by Novartis Vaccines and Diagnostics.
Inclusion Criteria:

 -  Provide written informed consent prior to initiation of any study procedures.

 -  Are able to understand and comply with planned study procedures and be available for
 all study visits.

 -  Are males or non-pregnant females, 19 to 64 years old, inclusive.

 -  Are in good health, as determined by vital signs (oral temperature, pulse, and blood
 pressure), medical history, and targeted physical examination based on medical history
 to ensure any existing medical diagnoses or conditions (except those in the Subject
 Exclusion Criteria) are stable . Subjects may be on chronic1 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. Note: Topical, nasal, and inhaled medications (with
 the exception of steroids as outlined in the Subjects Exclusion Criteria (see Section
 5.2), vitamins, and contraceptives are permitted.

 -  Oral temperature is less than 100.4 degrees F.

 -  Pulse is 50 to 115 bpm, inclusive.

 -  Systolic blood pressure is 85 to 150 mm Hg, inclusive.

 -  Diastolic blood pressure is 55 to 95 mmHg, inclusive.

 -  Erythrocyte sedimentation rate (ESR) is less than 30 mm per hour.

 -  Alanine aminotransferase (ALT) is less than 44 IU/L for females or is less than 61
 IU/L for males.

 -  Creatinine is less than 1.11 mg/dL for females or is less than 1.38 mg/dL for males.

 -  White blood cells (WBC) are greater than 3.9 x10^3/UL and less than 10.6 x10^3/UL.

 -  Hemoglobin is greater than 11.4 g/dL for females or is greater than 12.4 g/dL for
 males.

 -  Platelets are greater than 139 x10^3/UL and less than 416 x10^3/UL.

 -  Total bilirubin is less than 1.3 mg/dL.

 -  Female subjects of childbearing potential who are not surgically sterile via tubal
 sterilization, bilateral oophorectomy, or hysterectomy or who are not postmenopausal
 for >/= 1 year must agree to practice highly effective contraception that may include,
 but is not limited to, abstinence from intercourse with a male partner, monogamous
 relationship with a vasectomized partner, male condoms with the use of applied
 spermicide, intrauterine devices, and licensed hormonal methods with use of a highly
 effective method of contraception for a minimum of 30 days prior to study product
 exposure and agree to practice highly effective contraception for the duration of
 study product exposure, including 2 months (defined as 60 days) after the last study
 vaccination. A highly effective method of contraception is defined as one which
 results in a low failure rate (i.e., less than 1 percent per year) when used
 consistently and correctly. Method of contraception will be captured on the
 appropriate data collection form.

 -  Female subjects of childbearing potential must have a negative urine or serum
 pregnancy test within 24 hours prior to study vaccination.

 Exclusion Criteria:

 -  Have an acute illness within 72 hours prior to study vaccination.

 -  Have any condition that, in the opinion of the site principal investigator or
 appropriate sub-investigator, would place the subject at an unacceptable risk of
 injury, render the subject unable to meet the requirements of the protocol, or
 confound the interpretation of the results.

 -  Have an acute or chronic medical condition that, in the opinion of the site principal
 investigator or appropriate sub-investigator, would render vaccination unsafe, or
 would interfere with the evaluation of responses.

 -  Have immunosuppression as a result of an underlying illness or treatment, or use of
 anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study
 vaccination.

 -  Have known active neoplastic disease or a history of any hematologic malignancy.

 -  Have known HIV, hepatitis B, or hepatitis C infection.

 -  Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based
 adjuvants, or other components of the study vaccine.

 -  Have a history of severe reactions following previous immunization with licensed or
 unlicensed influenza virus vaccines.

 -  Have a personal or family history of narcolepsy with or without cataplexy.

 -  Have a history of Guillain-Barré Syndrome.

 -  Have a history of neuralgia, paresthesia, neuritis, convulsions, or encephalomyelitis
 within 90 days prior to study vaccination.

 -  Have a history of autoimmune disease, including but not limited to neuroinflammatory
 diseases, vasculitis, clotting disorders, dermatitis, arthritis, thyroiditis, or
 muscle, liver or kidney disease.

 -  Have a history of alcohol or drug abuse within 5 years 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.

 -  Have taken oral or parenteral corticosteroids of any dose within 30 days prior to
 study vaccination.

 -  Have taken high-dose inhaled corticosteroids within 30 days prior to study
 vaccination. High-dose defined as >800mcg/day of beclomethasone dipropionate CFC or
 equivalent.

 -  Received any licensed live vaccine within 30 days or any licensed inactivated vaccine
 within 14 days prior to the first study vaccination or planned receipt of any vaccine
 from the first study vaccination through the follow-up visit at approximately 21 days
 after the last study vaccination. This is inclusive of licensed seasonal influenza
 vaccines.

 -  Received immunoglobulin or other blood products (with exception of Rho D
 immunoglobulin) within 90 days prior to study vaccination.

 -  Received an experimental agent (vaccine, drug, biologic, device, blood product, or
 medication) within 30 days prior to the first study vaccination, or expects to receive
 an experimental agent other than from participation in this study during the 13-month
 study period.

 -  Are participating or plan to participate in another clinical trial with an
 interventional agent (licensed or unlicensed vaccine, drug, biologic, device, blood
 product, or medication) during the 13-month study period.

 -  Prior participation in a clinical trial of influenza A/H7 vaccine and assigned to a
 group receiving influenza A/H7 vaccine (does not apply to documented placebo
 recipients) or have a history of A/H7 actual or potential exposure or infection prior
 to the first study vaccination.

 -  Plan to travel outside the U.S. (continental U.S., Hawaii and Alaska) in the time
 between the first study vaccination and 42 days after the first study vaccination.

 -  Female subjects who are breastfeeding or plan to breastfeed at any given time from the
 first study vaccination until 30 days after their last study vaccination.

 -  Blood donation within 30 days prior to enrollment and within 30 days after the last
 blood draw (only for a subset of healthy adult subjects - all volunteers, 19-64 years
 old, enrolled at the Vanderbilt VTEU site, who consent to blood donation for the
 immunology exploratory assays).