Efficacy, Safety, and Immunogenicity of a Plant-Derived Quadrivalent Virus-Like Particles (VLPs) Influenza Vaccine in Adults
Condition: Virus Diseases; RNA Virus Infections; Respiratory Tract Diseases; Respiratory Tract Infections; Influenza
MeSH terms: Infections; Communicable Diseases; Virus Diseases; Influenza, Human; Respiratory Tract Infections; RNA Virus Infections; Respiratory Tract Diseases
Intervention: Quadrivalent VLP Vaccine; Placebo
Intervention description: Single dose of a 30 µg/strain of Quadrivalent VLP Vaccine; Single dose of a Placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Observer-blind
Enrollment: 10160.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Influenza; Human; RNA Virus Infections; Efficacy; Immunologic; Immunogenic Factors; Physiological Effects of Drug; Virus Diseases; Orthomyxoviridae Infections; Infection; Vaccine; Safety; Plant-made; Virus-like Particle; Hemagglutinin; Quadrivalent Influenza Vaccine

Summary:

      This Phase 3 study is intended to assess the efficacy of the Quadrivalent VLP Influenza
      Vaccine during the 2017-2018 influenza season in healthy adults 18 to 64 years of age. One
      dose of Quadrivalent VLP Influenza Vaccine (30 μg/strain) or of placebo will be administered
      to approximately 10,000 participants
    

Eligibility criteria:

        Inclusion Criteria

        Participants must meet all of the following inclusion criteria to be eligible for
        participation in this study; no protocol waivers are allowed:

          1. Participants must have a body mass index (BMI) below 40 kg/m^2;

          2. Participants are considered by the Investigator to be reliable and likely to cooperate
             with the assessment procedures and be available for the duration of the study;

          3. Participants must be in good general health prior to study participation, with no
             clinically relevant abnormalities that could jeopardize participant safety or
             interfere with study assessments, as assessed by the Principal Investigator or
             sub-Investigator (thereafter referred as Investigator) and determined by medical
             history, physical examination, and vital signs; Note: Participants with a pre-existing
             chronic disease will be allowed to participate if the disease is stable and, according
             to the Investigator's judgment, the condition is unlikely to confound the results of
             the study or pose additional risk to the participant by participating in the study.
             Stable disease is generally defined as no new onset or exacerbation of pre-existing
             chronic disease three months prior to vaccination. Based on the Investigator's
             judgment, a participant with more recent stabilization of a disease could also be
             eligible.

          4. Female participants must have a negative urine pregnancy test result at the
             Screening/Vaccination visit (Visit 1).

          5. Female participants of childbearing potential must use an effective method of
             contraception for one month prior to vaccination and agree to continue employing
             adequate birth control measures for at least 60 days post-vaccination. Moreover,
             female participants must have no plan to become pregnant for at least two months
             post-vaccination. Abstinent participants should be asked what method(s) they would use
             should their circumstances change, and participants without a well-defined plan should
             be excluded. The following relationship or methods of contraception are considered to
             be effective:

               -  Hormonal contraceptives (e.g. oral, injectable, topical [patch], or estrogenic
                  vaginal ring);

               -  Intra-uterine device with or without hormonal release;

               -  Male partner using a condom plus spermicide or sterilized partner (at least one
                  year prior to vaccination);

               -  Credible self-reported history of heterosexual vaginal intercourse abstinence
                  until at least 60 days post-vaccination;

               -  Female partner;

          6. Non-childbearing females are defined as:

               -  Surgically-sterile (defined as bilateral tubal ligation, hysterectomy or
                  bilateral oophorectomy performed more than one month prior to vaccination); or

               -  Post-menopausal (absence of menses for 24 consecutive months and age consistent
                  with natural cessation of ovulation).

        Exclusion Criteria:

        Participants who meet any of the following criteria will be excluded from participating in
        this study; no protocol waivers are allowed:

          1. Any participant whose medical condition(s) is sufficiently severe that annual
             influenza vaccination would be routinely recommended in the jurisdiction of
             recruitment, as per the Investigator's judgement;

          2. According to the Investigator's opinion, history of significant acute or chronic,
             uncontrolled medical or neuropsychiatric illness. 'Uncontrolled' is defined as:

               -  Requiring a new medical or surgical treatment during the three months prior to
                  study vaccine administration unless the criteria outlined in inclusion criterion
                  no. 5 can be met (i.e. the Investigator can justify inclusion based upon the
                  innocuous nature of medical/surgical events and/or treatments);

               -  Requiring any significant change in a chronic medication (i.e. drug, dose,
                  frequency) during the three months prior to study vaccine administration due to
                  uncontrolled symptoms or drug toxicity unless the innocuous nature of the
                  medication change meets the criteria outlined in inclusion criterion no. 5 and is
                  appropriately justified by the Investigator.

          3. Any medical or neuropsychiatric condition or any history of excessive alcohol use or
             drug abuse which, in the Investigator's opinion, would render the participant unable
             to provide informed consent or unable to provide valid safety observations and
             reporting;

          4. Any autoimmune disease other than hypothyroidism on stable replacement therapy
             (including, but not limited to rheumatoid arthritis, systemic lupus erythematosus,
             Crohn's disease, and inflammatory bowel disease) or any confirmed or suspected
             immunosuppressive condition or immunodeficiency including known or suspected human
             immunodeficiency virus (HIV), Hepatitis B or C infection, the presence of
             lymphoproliferative disease;

          5. History of chronic pulmonary (including asthma, bronchopulmonary dysplasia, and cystic
             fibrosis) or cardiovascular (except isolated hypertension), renal, hepatic,
             neurologic, hematologic (including anemia and hemoglobinopathy), or metabolic
             disorders (including diabetes mellitus);

          6. Because this is a placebo-controlled study, any participants in close contact with
             individuals considered to be at high risk for developing influenza-related
             complications (individuals considered at high risk for complications include adults
             and children who have chronic pulmonary or cardiovascular [except isolated
             hypertension], renal, hepatic, neurologic, hematologic, or metabolic disorders
             [including diabetes mellitus]).

          7. Administration or planned administration of any non-influenza vaccine within 30 days
             prior to randomization up to blood sampling on Day 21. Immunization on an emergency
             basis will be evaluated case-by-case by the Investigator;

          8. Administration of any adjuvanted or investigational influenza vaccine within one year
             prior to randomization or planned administration prior to the completion of the study;

          9. Administration of any 'standard', non-adjuvanted influenza vaccine (e.g. live
             attenuated trivalent/quadrivalent inactivated influenza vaccine or split
             trivalent/quadrivalent inactivated influenza vaccine administered by intranasal,
             intradermal, or intramuscular route) within six months prior to randomization and up
             to completion of the study;

         10. Use of any investigational or non-registered product within 30 days or five
             half-lives, whichever is longer, prior to randomization or planned use during the
             study period. Participants may not participate in any other investigational or
             marketed drug study while participating in this study until after the study;

         11. Treatment with systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or
             equivalent) per day for more than seven consecutive days or for 10 or more days in
             total, within one month of study vaccine administration; any other cytotoxic or
             immunosuppressant drug, or any immunoglobulin preparation within three months of
             vaccination and until the completion of the study. Low doses of nasal or inhaled
             glucocorticoids are allowed. Topical steroids are permitted;

         12. Any significant disorder of coagulation including, but not limited to, treatment with
             warfarin derivatives or heparin. Persons receiving prophylactic anti-platelet
             medications (e.g. low-dose aspirin [no more than 325 mg/day]), and without a
             clinically apparent bleeding tendency are eligible. Participants treated with new
             generation drugs that do not increase the risk of intramuscular bleeding (e.g.
             clopidogrel) are also eligible;

         13. History of allergy to any of the constituents of the Quadrivalent VLP Influenza
             Vaccine or tobacco;

         14. History of anaphylactic allergic reactions to plants or plants components;

         15. Use of antihistamines with systemic absorption for more than 14 days in the four weeks
             prior to vaccination or use of antihistamines 48 hours prior to study vaccination (the
             use of topical antihistamines and nasal or inhaled steroids is acceptable);

         16. Use of prophylactic medications (e.g. acetaminophen/paracetamol, aspirin, naproxen, or
             ibuprofen) within 24 hours of randomization to prevent or pre-empt symptoms due to
             vaccination. Any participant discovered to have taken a prophylactic medication to
             prevent or pre-empt symptoms due to vaccination within the 24 hours prior to planned
             randomization must be delayed until at least the 24 hours period is met;

         17. Planned use of influenza antiviral treatment medication before the collection of
             nasopharyngeal swabs (e.g. oseltamivir, zanamivir, rapivab);

         18. Have a rash, dermatological condition, tattoos, muscle mass, or any other
             abnormalities at the injection site that may interfere with injection site reaction
             rating;

         19. Participants who have received a blood transfusion within 90 days prior to study
             vaccination;

         20. Any female participant who has a positive or doubtful pregnancy test result prior to
             vaccination or who is lactating;

         21. Participants with abnormal vital signs (systolic blood pressure [BP] > 140 mmHg and/or
             diastolic BP ≥ 90 mmHg, heart rate ≤ 45 beats/min and ≥ 100 beats/min) evaluated by an
             Investigator to be clinically significant. A participant with abnormal vital signs
             results may be included in the study based on Investigator's judgment (e.g. a resting
             hear rate ≤ 45 in highly trained athletes);

         22. Presence of any febrile illness (including an oral temperature ≥ 38.0 ˚C within 24
             hours prior to vaccination. Such participants may be re-evaluated for enrolment after
             resolution of illness;

         23. Cancer or treatment for cancer within three years prior to study vaccine
             administration.

             Persons with a history of cancer who are disease-free without treatment for three
             years or more are eligible. However, individuals with conditions such as treated and
             uncomplicated basal cell carcinoma of the skin or non-treated, non-disseminated local
             prostate cancer may be eligible;

         24. Participants identified as an Investigator or employee of the Investigator or clinical
             site with direct involvement in the proposed study, or identified as an immediate
             family member (i.e. parent, spouse, natural or adopted child) of the Investigator or
             employee with direct involvement in the proposed study or any employee of Medicago;

         25. Participants with a history of Guillain-Barré Syndrome.