Two Doses of Multimeric-001 (M-001) Followed by Influenza Vaccine
Condition: Influenza; Influenza Immunisation
MeSH terms: Influenza, Human
Intervention: Influenza Multimeric-001 Vaccine; Placebo; Quadrivalent Recombinant Seasonal Influenza Vaccine
Intervention description: The M-001 vaccine consists of 3 repetitions of 9 conserved linear epitopes that are prepared as a single recombinant protein. The M-001 vaccine is expected to protect against existing as well as future seasonal and pandemic virus strains.; Placebo is saline injection; Quadrivalent Inactivated Influenza Vaccine (IIV4) for intramuscular injection is indicated for active immunization against influenza disease caused by influenza virus subtypes A and type B present in the vaccine.
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 120.0
Sex: All
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Immunogenicity; Influenza Vaccine; M-001 vaccine; Reactogenicity; Safety

Summary:

      This is a Phase II randomized, double-blind, placebo-controlled trial in 120 males and
      non-pregnant females, 18 to 49 years old, inclusive, who are in good health and meet all
      eligibility criteria. This clinical trial will be conducted at 3 United States sites and is
      designed to assess the safety, reactogenicity, and immunogenicity of two priming doses of
      M-001 followed by a seasonal quadrivalent inactivated influenza vaccine (IIV4). The duration
      of this trial for each subject will be approximately 7 months. The entire study duration will
      be approximately 24 months. The primary objectives are: 1) To assess the safety as measured
      by vaccine related adverse events, reactogenicity, and laboratory adverse events of two doses
      of M-001 vaccine, each dose administered approximately 21 days apart; and 2) To assess the T
      cell responses to M-001 component peptides following two doses of M-001.
    

Eligibility criteria:

        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 non-pregnant females, 18 to 49 years old, inclusive.

          4. Are in good health*.

             *As determined by medical history and targeted 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 prior to investigational
             vaccine study product administration. 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 and investigational vaccine
             study product administration. 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 investigational study product vaccination are acceptable
             provided there was no deterioration in the subject's chronic medical condition that
             necessitated a medication change. All chronic medical condtions should pose 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 inhaled corticosteroids as outlined in the Subject Exclusion Criteria), herbals,
             vitamins, and supplements are permitted.

          5. Oral temperature is less than 100.0 degrees F.

          6. Pulse** is 50 to 100 bpm, inclusive.

             **Acceptable pulse range prior to IIV4 dose is 45 to 115 bpm, inclusive and no
             symptoms.

          7. Systolic blood pressure*** is 85 to 150 mmHg, inclusive. ***Acceptable systolic blood
             pressure range prior to IIV4 dose is 80 to 155 mm Hg, inclusive and no symptoms.

          8. Diastolic blood pressure**** is 55 to 95 mmHg, inclusive.

             ****Acceptable diastolic blood pressure range prior to IIV4 dose is 50 to 100 mm Hg,
             inclusive and no symptoms.

          9. Women of childbearing potential* must use an acceptable method of contraception** from
             30 days prior to vaccination until 60 days after the second of dose of M-001 or
             placebo.

         10. Women of childbearing potential***** must use an acceptable method of
             contraception****** from 30 days prior to receipt of IIV vaccination, and must plan to
             use until 28 days after the IIV.

             *****Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy, or
             successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization
             with history of documented radiological confirmation test achieved or with use of
             another approved birth control method if confirmation test not confirmed) and still
             menstruating or < 1 year of the last menses if menopausal).

             ******Includes, but is not limited to, non-male sexual relationships, abstinence from
             sexual intercourse with a male partner, monogamous relationship with a vasectomized
             partner, 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.

         11. Female subjects of childbearing potential must have a negative urine or serum
             pregnancy test within 24 hours prior to study vaccination.

        Exclusion Criteria:

          1. Have an acute illness*, as determined by the site PI or appropriate sub-investigator,
             within 72 hours prior to 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 known hypersensitivity or allergy to eggs, egg or chicken protein, or other
             components of the study vaccine.

          7. Have a history of severe reactions following previous immunization with licensed or
             unlicensed influenza vaccines.

          8. Have a history of Guillain-Barré Syndrome.

          9. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.

         10. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other
             psychiatric diagnosis that may interfere with subject compliance or safety
             evaluations.

         11. 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.

         12. Have taken oral or parenteral (including intraarticular) corticosteroids of any dose
             within 30 days prior to study vaccination.

         13. Have taken high-dose*** 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/health-pro/guidelines/current/asthma-guidelines/quick-refere
             nce-html#estimated-comparative-daily-doses.

             ****Topical and nasal steroids are permissible.

         14. Received any licensed live vaccine or plan to receive a licensed live vaccine within
             30 days prior or 21 days after each M-001 study vaccination.

         15. Received a licensed inactivated vaccine within 14 days prior to or 21 days after each
             M-001 study vaccination.

         16. Plans to or received the current 2018-2019 influenza vaccine (inactivated or live
             prior to ordering the study (the 2018-2019 influenza vaccine will be given during the
             trial.))

         17. Received immunoglobulin or other blood products (with exception of Rho D
             immunoglobulin) within 90 days prior to study vaccination.

         18. Received an experimental agent***** within 30 days prior to the first study
             vaccination, or expects to receive an experimental agent****** during the 7-month
             trial-reporting period.

             *****Including vaccine, drug, biologic, device, blood product, or medication.

             ******Other than from participation in this study.

         19. Are participating or plan to participate in another clinical trial with an
             interventional agent******* that will be received during the 7-month trial-reporting
             period.

             *******Including agent (licensed or unlicensed vaccine, drug, biologic, device, blood
             product, or medication) during the 9-month study period.

         20. Plan to travel outside the U.S. (continental U.S., Hawaii and Alaska) in the time
             between the first study vaccination and 21 days after the last study
             vaccination********.

             ********Study vaccination refers to investigational study product vaccination.

         21. Female subjects who are breastfeeding or plan to breastfeed at any given time from the
             first study vaccination until 30 days after the last study vaccination.

         22. Blood donation or planned blood donation within 30 days prior to the study vaccination
             through 30 days after the last blood drawn for this study.

         23. 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.

         24. Have a history of convulsions or encephalomyelitis within 90 days prior to study
             vaccination.