The purpose of this study is to evaluate the safety, tolerance, and immunogenicity of
MAS-1-Adjuvanted seasonal inactivated influenza vaccine (IIV) (MER4101) with hemagglutinin
dose escalation compared to non-adjuvanted comparator IIV standard dose (SD) in healthy
adults and high dose (HD) IIV in ambulatory elderly subjects.
Hypothesis: Reduced hemagglutinin (HA) dose IIV formulated in MAS-1 adjuvant (MER4101) is
safe, tolerable and immunogenic in healthy young adults 18 - 49 years of age compared to SD
IIV and an optimal dose of HA formulated in MAS-1 adjuvant will be safe and immunogenic in
adults who are 65 years of age and older compared to HD IIV (from Phase 1A, known to be 9µg
of HA antigen).
The proposed study is a phase IA/B 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 will evaluate 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 will evaluate the optimal dose of IIV in
MAS-1 selected under phase IA (known to be 9µg of HA antigen) for safety, tolerability and
HAI antibody response in ambulatory elderly subjects compared to high dose (HD) IIV.
The ability of SD IIV to protect against seasonal influenza virus infection in the elderly
is less than vaccine efficacy observed in healthy young adults. The proposed
MAS-1-adjuvanted influenza virus vaccine offers the potential for higher seroconversion and
seroprotection rates, higher antibody levels, prolonged duration of protective antibodies,
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
Specifically Phase IA:
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.
Specifically Phase 1B:
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
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 Both Phase 1A and Phase 1B:
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
Specifically Phase IA:
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.
Specifically Phase 1B:
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.
For Both Phase 1A and Phase 1B:
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
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.
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
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
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
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
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
30. Personal or family history of narcolepsy with or without cataplexy.