H7N9 Mix and Match With MF59 in Healthy Elderly Persons

This is a Phase II randomized, partially-blinded, controlled trial in males and females, 65
years of age and older, who are in good health and meet all eligibility criteria. This
clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a
monovalent inactivated influenza A/H7N9 virus vaccine, derived from the influenza
A/Shanghai/2/2013 virus, manufactured by Sanofi Pasteur administered intramuscularly at
different intervals and dosages (3.75, 7.5, or 15 mcg of HA/0.5 mL dose) given with MF59
adjuvant manufactured by Novartis Vaccines and Diagnostics. Subjects will be assigned
randomly to 1 of 6 groups (60 to 100 subjects per group) to receive three doses
intramuscularly of the inactivated A/H7N9 vaccine at dosages (3.75, 7.5, or 15 mcg of HA/0.5
mL dose) given with MF59 adjuvant using two different study vaccination schedules. The first
and third study vaccinations will be administered to all subjects on Day 1 and approximately
Day 169. The second study vaccination will be administered either on approximately Day 29
for Groups 1, 3, and 5 or approximately Day 57 for Groups 2, 4, and 6. Reactogenicity will
be measured from the time of each study vaccination through 8 days after each study
vaccination by the occurrence of solicited injection site and systemic reactions.
Unsolicited non-serious adverse events (AEs) will be collected from the time of each study
vaccination through approximately 28 days after each study vaccination. Serious adverse
events (SAEs) and new-onset chronic medical conditions will be collected from the time of
the first study vaccination through approximately 12 months after the last study
vaccination.

Immunogenicity testing will include performing hemagglutination inhibition (HAI) and
neutralizing (Neut) antibody assays on serum obtained immediately prior to the first study
vaccination (Day 1), approximately 28 days after the second study vaccination (approximately
Day 57 for Groups 1, 3, and 5; approximately Day 85 for Groups 2, 4, and 6), immediately
prior to the third study vaccination (approximately Day 169), and approximately 28 days
after the third study vaccination (approximately Day 197). Subjects in Groups 1, 3, and 5
will also have immunogenicity testing for HAI and Neut antibody assays performed on serum
obtained at approximately 56 days after the second study vaccination (approximately Day 85).
Between 360 and 600 subjects will be enrolled in this trial.

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 females, 65 years of age and older.

4. Are in good health1. 1As determined by medical history and targeted physical
examination, if indicated based on medical history, to evaluate acute or currently
ongoing chronic medical diagnoses or conditions that would affect the assessment of
eligibility and safety of subjects. Chronic medical diagnoses or conditions being
actively managed must be within acceptable limits in the last 180 days. Good health
in the elderly is also defined as no change in chronic prescription medication, dose,
or frequency of medication in the 90 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 does not indicate a worsening of medical
diagnosis or condition. Similarly, medication changes subsequent to enrollment and
first study vaccination are acceptable provided the subject is asymptomatic,
condition stable, 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 steroids as outlined in the Subject Exclusion
Criteria (see Section 5.2)), herbals, vitamins, and supplements are permitted

5. Oral temperature is less than 100.0 degrees F.

6. Pulse is 50 to 115 bpm, inclusive.

7. Systolic blood pressure is 85 to 160 mm Hg, inclusive.

8. Diastolic blood pressure is 55 to 95 mm Hg, inclusive

Exclusion Criteria:

1. Have an acute illness2, as determined by the site principal investigator or appropriate
sub-investigator, within 72 hours prior to study vaccination.

2An 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
participation3.

3Including acute or chronic medical disease or condition, defined as persisting 3 months
(defined as 90 days) or longer, 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
study.

3. Reside in a nursing home4 or other skilled nursing facility or have a requirement for
skilled nursing care.

4An ambulatory subject who does not require skilled nursing care and is a resident of a
retirement home or community is eligible for this clinical trial.

4. Inability to provide informed consent or complete study activities, for example, due to
dementia or other impairment.

5. 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.

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

7. Have known HIV, hepatitis B, or hepatitis C infection. 8. Have known hypersensitivity
or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components
of the study vaccine.

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

10. Have a history of Guillain-Barré Syndrome. 11. Have a history of neuralgia,
paresthesia, neuritis, convulsions, or encephalomyelitis within 90 days prior to study
vaccination.

12. Have a history of autoimmune disease5. 5Including, but not limited to, autoimmune
processes resulting in neuroinflammatory diseases, vasculitis, clotting disorders,
dermatitis, arthritis, thyroiditis, or muscle, liver, or kidney disease.

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 corticosteroids of any dose within 30 days prior to
study vaccination.

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

18. Received a licensed live vaccine within 30 days prior to enrollment in this study, or
plans to receive a licensed live vaccine within 30 days before or after each study
vaccine.

19. Received a licensed inactivated vaccine within 14 days prior to enrollment in this
study, or plans to receive a licensed inactivated vaccine within 14 days before or after
each study vaccine.

20. Received immunoglobulin or other blood products within 90 days prior to study
vaccination.

21. Received an experimental agent6 within 30 days prior to the first study vaccination,
or expects to receive an experimental agent7 during the 18-month study period.

6Including vaccine, drug, biologic, device, blood product, or medication. 7Other than from
participation in this study. 22. Are participating or plan to participate in another
clinical trial with an interventional agent8 during the 18-month study period.

8 Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or
medication.

23. Prior participation in a clinical trial of influenza A/H7 vaccine9 or have a history
of A/H7 actual or potential exposure or infection prior to the first study vaccination.

9And assigned to a group receiving influenza A/H7 vaccine, does not apply to documented
placebo recipients.

24. Plan to travel outside the US (continental US, Hawaii, and Alaska) within the 28 days
following each study vaccination.