Safety and Immunogenicity Study of an Influenza Vaccination Strategy Including an H3N2 M2SR Prime Followed by a Seasonal Quadrivalent Inactivated Vaccine Boost in a Pediatric Population 9-17 Years Old

This is a Phase I double-blind, randomized, placebo-controlled study in 50 healthy
adolescents and children, 9-17 years of age, inclusive, who are in good health and meet all
eligibility criteria. This clinical trial is designed to assess the safety and immunogenicity
of a prime-boost regimen of H3N2 M2SR intranasal influenza vaccine (manufactured by FluGen)
followed by licensed inactivated Quadrivalent Influenza Vaccine (QIV) boost administered
intramuscularly. Subjects will be enrolled in one of two groups in a 1:1 ratio. Arm 1 will
receive one dose of M2SR intranasally on Day 1 and one dose of QIV on Day 92. Arm 2 will
receive one dose of placebo (saline) intranasally on Day 1, and one dose of QIV on Day 92.
Study duration will be approximately 28 months with patient participation duration
approximately 13 months. The primary study objective is to assess the safety and
reactogenicity of a monovalent live attenuated influenza H3N2 M2SR vaccine. The secondary
study objectives are to identify circulating and mucosal antibody responses induced by H3N2
M2SR vaccination and to identify cellular immune responses induced by H3N2 M2SR vaccination.

Inclusion Criteria:

1. Parent(s)/legal guardian(s) must provide written informed consent prior to initiation
of any study procedures, and subject must provide assent.

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

3. Are males or non-pregnant females, 9-17 years old, inclusive at the time of
enrollment.

4. 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, ER, or urgent
care for condition and no adverse symptoms that need medical intervention). 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 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 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: Low dose topical steroids, herbals, vitamins, and
supplements are permitted.

5. Oral temperature is less than 100.0 degrees Fahrenheit.

6. For female adolescent of child-bearing potential* must agree to correctly use an
acceptable method of contraception** from 30 days prior to vaccination until 30 days
after the last study vaccination.

*Defined by the onset of menses, and not sterilized via tubal ligation, bilateral
oophorectomy, 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.

**Includes non-male sexual relationships, abstinence from sexual intercourse with a
male partner, monogamous relationship with a vasectomized partner, and correct use of
male condoms with the use of applied spermicide, intrauterine devices, NuvaRing(R),
and licensed hormonal methods such as implants, injectables, contraceptive patches or
oral contraceptives ("the pill"). Method of contraception will be captured on the
appropriate data collection form.

7. Female adolescent of childbearing potential must have a negative urine pregnancy test
within 24 hours prior to study vaccination.

8. Males who are sexually active with a female of childbearing potential must agree not
to father a child for 30 days after receipt of the first study vaccination.

9. Agrees not to participate in another clinical trial during the study period.

10. Agrees not to donate blood or blood products to a blood bank for 12 months after
receiving the investigational vaccine.

11. Weight = / > 34 kg or 75 pounds.

12. Hemoglobin = / > 11.5 g/dL.

13. Hematocrit > 35%.

14. Ferritin level > 15 ng/mL.

15. Parent/legal guardian must provide consent to future use of stored samples.

Exclusion Criteria:

1. Have an acute illness*, as determined by the site PI or appropriate sub-investigator,
within 72 hours prior to each 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 study.

3. 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.

4. Have known active neoplastic disease or a history of any hematologic malignancy.
Non-melanoma skin cancers that are not active are permitted.

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

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

7. History of anatomic disorder of the nares or nasopharynx (Deviated septum is allowed).

8. History of chronic sinus infections.

9. Have a history of Guillain-Barre Syndrome.

10. Have a history of alcohol or drug abuse prior to study vaccination.

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

12. Have been hospitalized for psychiatric illness, history of suicide attempt, or
confinement for danger to self or others prior to study vaccination.

13. Have taken oral and/or nasal corticosteroids of any dose within 30 days prior to each
study vaccination or plan to take in the 30 days following the first study
vaccination.

14. 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.

**https://www.nhlbi.nih.gov/files/docs/guidelines/asthma_org.pdf.

15. Use of aspirin or salicylate-containing products 30 days prior to the first
vaccination.

16. Recurring or active wheezing or diagnosis of asthma, or history of significant
wheezing*.

*Medically significant wheezing: defined as wheezing on physical exam plus sign of
respiratory distress (tachypnea, retractions, or dyspnea), hypoxemia (O2 saturation <
95%), or new bronchodilator prescription, or use of daily bronchodilator therapy (not
on an "as needed" basis).

17. Received any licensed live or inactivated vaccine within 30 days prior to or plan to
receive any licensed live or inactivated vaccine within 30 days after each study
vaccination.

18. Received any influenza vaccine (inactivated or live) within 6 months prior to the
first study vaccination and until the end of the study.

19. Received immunoglobulin or other blood products within 6 months prior to study
vaccination.

20. Received an experimental agent* within 30 days prior to the first study vaccination,
or expects to receive an experimental agent** during the 12-month trial-reporting
period.

*Including vaccine, drug, biologic, device, blood product, or medication.

**Other than from participation in this study.

21. Are participating or plan to participate in another clinical trial with an
interventional agent* that will be received during the 12-month trial-reporting
period.

*Including agent (licensed or unlicensed vaccine, drug, biologic, device, blood
product, or medication) during the 12-month study period.

22. Prior history of H3N2 actual or potential exposure or infection prior to the first
study vaccination, or receipt of experimental vaccines within the past year prior to
the first study vaccine.

23. Female adolescent subject who is breastfeeding or plans to breastfeed at any given
time from the first study vaccination until 30 days after the last study vaccination.

24. Blood donation within 30 days prior to the study vaccination through 30 days after the
last blood drawn for this study.

25. Have signs or symptoms that could confound or confuse assessment of study vaccine
reactogenicity*.

*The study vaccination should be postponed/deferred until signs or symptoms have
resolved and if within the acceptable protocol-specified window for that visit.

26. Have received any antiviral drug within 3 days of study vaccination.