H3N2 M2SR in Pediatric Population
Condition: Influenza; Influenza Immunisation
MeSH terms: Influenza, Human
Intervention: Influenza Virus Monovalent A/H3N2/Bris 10 M2SR Live Vaccine; Placebo; Quadrivalent MDCK Inactivated Influenza Vaccine
Intervention description: Live monovalent influenza A/H3N2-based M2SR (M2 defective Single Replication vaccine), comprised of 5 out of 8 gene segments on the donor virus influenza A/Puerto Rica/8/34. HA and NA derive from an A/Brisbane/10/2007-like virus. Administered intranasally as s single dose.; H3N2 M2SR vaccine placebo (normal saline). Administered intranasally as a single dose.; A quadrivalent cell culture inactivated vaccine (ccIV4) is an inactivated subunit influenza vaccine prepared from virus propagated in Madin Darby Canine Kidney (MDCK) cells indicated for the prevention of influenza disease caused by influenza virus subtypes A and type B contained in the vaccine. Administered intramuscularly as a single dose.
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 43.0
Sex: All
Minimum age: 9 Years
Maximum age: 17 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: H3N2 M2SR Prime; Immunogenicity; Influenza; Pediatric Population; QIV; Safety; Vaccine

Summary:

      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.
    

Eligibility criteria:

        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.