The Safety, Tolerance, and Immunogenicity of MAS-1-Adjuvanted Seasonal Inactivated Influenza Vaccine (MER4101)

The study is a Phase 1A, 1B and 1B extension, randomized, double-blind, single-center,
clinical trial, in healthy adults (18-49 years old) and ambulatory elderly subjects (aged 65
years and older). Phase IA evaluated the safety, tolerability and hemagglutination inhibition
assay (HAI) antibody response of each of four escalating doses of influenza hemagglutinin
(HA) antigen with a fixed dose of a water-in-oil emulsion adjuvant MAS-1 (Mercia Adjuvant
System-1), compared with licensed, unadjuvanted, standard dose (SD) of licensed inactivated
trivalent influenza virus vaccine (IIV). Phase IB evaluated the optimal dose of IIV in MAS-1
selected under phase IA for safety, tolerability and HAI antibody response (from Phase 1A
known to be 9 µg of HA antigen in 0.3 mL dose of MAS-1 adjuvanted emulsion) in ambulatory
elderly subjects compared to high dose (HD) IIV. The Phase 1B extension will evaluate if the
increased dose volume of MAS-1 (0.5 mL vs 0.3 mL) at the same 9 µg/HA adjuvanted IIV vaccine
is safe, well tolerated and immunogenic, and then whether the increased dose of 15 µg/HA in
0.5 mL MAS-1 is safe, well tolerated and still more immunogenic in elderly subjects.

The ability of standard dose (SD) IIV to protect against seasonal influenza virus infection
in the elderly is less than vaccine efficacy observed in healthy young adults. The
MAS-1-adjuvanted influenza virus vaccine offers the potential for higher seroconversion and
seroprotection rates, higher antibody levels, prolonged duration of protective antibodies,
hemagglutinin (HA) antigen dose-sparing and cross-protection against antigenically divergent
viral strains. This study will determine if the adjuvanted vaccine formulated with one or
more of the reduced HA antigen doses is safe. The study will also determine if it is likely
to induce an improved HA antibody response (HAI) when compared to SD IIV in healthy adults
and HD IIV in elderly subjects. This trial will inform future clinical trials in at-risk
populations of older patients

Inclusion Criteria:

Specifically Phase 1A:

1. Males or non-pregnant females, 18 to 49 years old, inclusive.

2. Female subjects of childbearing potential who must agree to practice avoidance of
pregnancy, including use of acceptable forms of contraception.

3. Pulse is 55 to 100 bpm, inclusive.

4. Systolic blood pressure is 90 to 140 mmHg, inclusive.

5. Diastolic blood pressure is 55 to 90 mmHg, inclusive.

For Phase 1B and Phase 1B Extension:

1. Ambulatory persons aged at least 65 years or older on the day of enrollment. Subjects
will be considered ambulatory if they are not institutionalized, bedridden, or
homebound.

2. Pulse is 50 to 115 bpm, inclusive.

3. Systolic blood pressure is 85 to 160 mmHg, inclusive.

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

For Phase 1A, Phase 1B, and Phase 1B Extension:

1. Written informed consent form and Authorization to Obtain and Release Protected Health
Information (HIPAA) form signed, 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 in good health, as determined by vital signs, medical history, and physical
examination based on medical history to ensure any existing medical diagnoses or
conditions are stable.

4. Stable chronic medical condition

5. Oral temperature is less than 100.4°F

6. Within institutional normal ranges for safety labs

7. Have a Body Mass Index (BMI) of 18-35

Exclusion Criteria:

Specifically Phase 1A:

1. Female subjects who are breastfeeding or plan to breastfeed at any given time from the
study vaccination until 30 days after the study vaccination will be ineligible

2. Receipt of 2014-2015 and 2015-2016 seasonal influenza vaccine.

3. After 03 September 2015, any subject who intends to receive the 2015-2016 licensed
influenza vaccine within 3 months after receiving study vaccination.

4. After 03 September 2015, any subject who has household contact with infants less than
1 year of age, persons 65 years of age and older, or immunocompromised individuals.

For Phase 1B and Phase 1B Extension:

1. Receipt of seasonal influenza vaccine in the past six months and planned receipt of
seasonal influenza vaccine within 3 months after receiving study vaccination.

Specifically Phase 1B Extension:

1. History of medically-attended altered mental status or inner ear (not including
hearing loss), labyrinth and cerebellar disorders within 3 months prior to enrollment.

2. Use of concomitant medications that may be nephrotoxic as judged by the investigator.

For Phase 1A, Phase 1B and Phase 1B Extension:

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

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

3. An acute febrile illness within 24 hours prior to vaccination. Vaccination will be
deferred until the participant has been afebrile for at least 24 hours.

4. Signs and symptoms of an acute infectious respiratory illness. Vaccination will be
deferred until the symptoms resolve.

5. 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.

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

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

8. Thrombocytopenia or bleeding disorder contraindicating IM vaccination. Receipt of
anticoagulants in the three weeks preceding inclusion.

9. Positive screen for HIV, hepatitis B, or hepatitis C infection.

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

11. Have a history of severe or life threatening reactions following previous immunization
with licensed or unlicensed influenza virus vaccines or a vaccine containing any of
the same substances.

12. Have a history of Guillain-Barré Syndrome.

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

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

15. Have a history of kidney disease or use of concomitant nephrotoxic medications.

16. Have a history of alcohol or drug abuse within 5 years prior to study vaccination or
drug addiction that may interfere with trial procedures.

17. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other
psychiatric diagnosis that may interfere with subject compliance or safety
evaluations.

18. 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.

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

20. Continuous or sporadic use of oral prednisone in the 90 days preceding vaccination.

21. 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.

22. Planned receipt of another vaccine in the four weeks following the trial vaccination.

23. Received any licensed live vaccine within 30 days prior to the study vaccination or
planned receipt from the study vaccination through 28 days after the study
vaccination.

24. Received any licensed inactivated vaccine within 14 days prior to the study
vaccination or planned receipt from the day of study vaccination through 28 days after
the study vaccination.

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

26. Received an experimental agent within 30 days prior to the study vaccination, or
expects to receive an experimental agent, other than from participation in this study,
during the study period.

27. Are participating or plan to participate in another clinical trial with an
interventional agent during the study period.

28. Plan to travel outside the U.S. (continental U.S., Hawaii and Alaska) within the 28
days following study vaccination.

29. Blood donation within 30 days prior to enrollment and within 30 days after the last
blood draw.

30. Personal or family history of narcolepsy with or without cataplexy.