Efficacy of a Plant-derived Quadrivalent Virus-like Particle (VLP) Vaccine in the Elderly
Condition: Virus Diseases; RNA Virus Infections; Respiratory Tract Diseases; Respiratory Tract Infections
MeSH terms: Infections; Communicable Diseases; Virus Diseases; Respiratory Tract Infections; RNA Virus Infections; Respiratory Tract Diseases
Intervention: Quadrivalent VLP Vaccine; Fluarix Quadrivalent® Comparator Vaccine
Intervention description: Single dose of a 30 µg/strain of Quadrivalent VLP Vaccine; Single dose of a 15 μg/strain of Fluarix Quadrivalent® Comparator Vaccine
Intervention MeSH terms: Vaccines
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a randomized, observer-blind, active comparator-controlled, multicenter, Phase 3 efficacy study.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Surveillance personnel is blinded from investigational product injection
Enrollment: 12794.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: vaccine; safety; efficacy; plant-made; virus-like particle; hemagglutinin

Summary:

      This Phase 3 study was intended to assess the relative efficacy of the Quadrivalent VLP
      Influenza Vaccine during the 2018-2019 influenza season compared to a licensed vaccine in
      elderly adults 65 years of age and older. One dose of VLP Influenza Vaccine (30 μg/strain) or
      of Comparator (15 μg/strain) was to be administered to 12,738 participants.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participants must have read, understood, and signed the informed consent form (ICF)
             prior to participating in the study; participants must also complete study-related
             procedures and communicate with the study staff at visits and by phone during the
             study;

          2. Participants must have a body mass index (BMI) ≤35 kg/m^2;

          3. 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;

          4. Male and female participants must be 65 years of age and older at the
             Screening/Vaccination visit (Visit 1);

          5. Participants must be non-institutionalized (e.g. not living in rehabilitation centres
             or old-age homes; living in an elderly community is acceptable) and have no acute or
             evolving medical problems prior to study participation and 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 are 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.

        Exclusion Criteria:

          1. According to the Investigator's opinion, history of an ongoing acute or evolving
             medical or neuropsychiatric illness. 'Evolving' was 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.

          2. Any medical or neuropsychiatric condition or any history of excessive alcohol use or
             drug abuse that would render the participant unable to provide informed consent or
             unable to provide valid safety observations and reporting, including methadone
             (methadone as treatment for opioid dependence may be acceptable if the participant has
             been otherwise opioid-free for at least three years);

          3. Any autoimmune disease other than hypothyroidism on stable replacement therapy
             (including, but not limited to rheumatoid arthritis, systemic lupus erythematosus,
             Crohn's disease, type 1 diabetes, 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;

          4. Any history of status asthmaticus or ongoing serious problems with asthma,
             hospitalization for asthma control, or recurrent asthma episodes requiring medical
             attention in the last three years (one or more episodes per year);

          5. 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 was evaluated case-by-case by the Investigator;

          6. Administration of any adjuvanted or investigational influenza vaccine within one year
             prior to randomization or planned administration prior to the completion of the study;

          7. 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 IM route) within six months prior to randomization and up to
             completion of the study;

          8. 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;

          9. Treatment with systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or
             equivalent) per day for more than seven consecutive days or for ten 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;

         10. 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 100 mg/day]), and without a
             clinically apparent bleeding tendency are eligible. Participants treated with new
             generation drugs that do not increase the risk of IM bleeding (e.g. clopidogrel) are
             also eligible;

         11. History of allergy to any of the constituents of the Quadrivalent VLP Influenza
             Vaccine, any components of the active comparator quadrivalent vaccine, or tobacco;

         12. History of anaphylactic allergic reactions to plants or plants components (including
             fruits and nuts);

         13. Use of antihistamines within 48 hours prior to study vaccination;

         14. Daily use of large doses of medication for pain control or inflammation (e.g. opioids,
             nonsteroidal anti-inflammatory drugs [NSAIDs]). Use of a singular regular dose either
             in the morning or at bedtime would not be exclusionary;

         15. 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;

         16. Planned use of influenza antiviral treatment medication before the collection of
             nasopharyngeal (NP) swabs (e.g. oseltamivir, zanamivir, rapivab);

         17. Have a rash, dermatological condition, tattoos, muscle mass, or any other
             abnormalities at the injection site that may interfere with injection site reaction
             rating;

         18. Participants who have received a blood transfusion within 90 days prior to study
             vaccination;

         19. Participants with abnormal vital signs (systolic blood pressure [BP] ≥ 150 mmHg and/or
             diastolic BP ≥ 95 mmHg for individuals taking antihypertensive medication and ≥ 140
             mmHg and/or diastolic BP ≥ 90 mmHg for individuals not taking antihypertensive
             medication; heart rate [HR] ≤ 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
             HR ≤ 45 in highly trained athletes);

         20. Presence of any febrile illness (including an oral temperature [OT] ≥ 38.0 ˚C within
             24 hours prior to vaccination;

         21. 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;

         22. 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) of the Investigator or any employee of Medicago
             (or their family members);

         23. Participants with a history of Guillain-Barré Syndrome.