Lot-to-lot Consistency of a Plant-Derived Quadrivalent Virus-Like Particles Influenza Vaccine in Healthy Adults
Condition: Virus Diseases; RNA Virus Infections; Respiratory Tract Infections; Respiratory Tract Disease; Influenza
MeSH terms: Infections; Communicable Diseases; Virus Diseases; Influenza, Human; Respiratory Tract Infections; RNA Virus Infections; Respiratory Tract Diseases
Intervention: Quadrivalent VLP Influenza Vaccine
Intervention description: Single dose of 30 µg/strain Quadrivalent VLP Influenza Vaccine
Phase: Phase 3
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Observer-blind
Enrollment: 1202.0
Sex: All
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Influenza; Human; RNA Virus Infections; Lot Consistency; Immunologic; Orthomyxoviridae Infections; Infection; Virus Diseases; Vaccine; Safety; Plant-made; Virus-like particle; Hemagglutinin

Summary:

      This Phase 3 study is intended to assess the clinical lot-to-lot consistency in manufacturing
      by evaluating and comparing the immunogenicity of three consecutively manufactured lots of
      the Quadrivalent Virus-Like Particles (VLP) Influenza Vaccine, during the 2016-2017 influenza
      season, in healthy adults 18-49 years of age. A single dose of one of three consecutive lots
      of Quadrivalent VLP Influenza Vaccine (30 µg/strain) will be administered to 1,200
      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 be considered by the Investigator to be reliable and likely to
             cooperate with the assessment procedures and be available for the duration of the
             study;

          2. Participants have a body mass index (BMI) ≤ 40.0 kg/m^2 on Day 0 (pre-vaccination);

          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 six months prior to vaccination. Based on the Investigator's judgment,
             a participant with a 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 the duration of the study. 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 a sterilized partner (at least one
                  year prior to vaccination);

               -  Credible self-reported history of heterosexual vaginal intercourse abstinence
                  until at least the Day 21 visit;

               -  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. 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 six months prior to
                  study vaccine administration unless the criteria outlined in inclusion criterion
                  no. 3 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 which, in the Investigator's opinion, would render the participant unable
             to provide informed consent or unable to provide valid safety observations and
             reporting;

          3. Any autoimmune disease other than hypothyroidism with stable replacement therapy; or
             any confirmed or suspected immunosuppressive condition or immunodeficiency including
             known or suspected human immunodeficiency virus (HIV), hepatitis B or C infection, or
             the presence of lymphoproliferative disease;

          4. Administration or planned administration of any non-influenza vaccine within 30 days
             prior to randomization and up to blood sampling on Day 21. Immunization on an
             emergency basis will be evaluated case-by-case by the Investigator;

          5. Administration of any adjuvanted or investigational influenza vaccine within 24 months
             prior to randomization or planned administration prior to the completion of Day 21;

          6. Administration of any "standard", non-adjuvanted influenza vaccine (e.g. live
             attenuated trivalent/quadrivalent inactivated influenza vaccine intranasal or split
             trivalent/quadrivalent inactivated influenza vaccine by either intradermal or IM
             route) within 24 months prior to randomization and up to completion of the Day 21
             visit;

          7. Use of any investigational or non-registered product within 30 days 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 the Day 21 visit. Participation in observational studies is permitted;

          8. Treatment with systemic glucocorticoids at a dose exceeding 10 milligrams (mg) of
             prednisone (or the equivalent) per day for more than seven consecutive days or for ten
             or more days in total, within one month of study vaccine administration; or any other
             cytotoxic or immunosuppressant drug, or any immunoglobulin preparation within three
             months of vaccination and until the completion of the Day 21 visit. Low doses of nasal
             or inhaled glucocorticoids and topical steroids are permitted;

          9. 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 IM bleeding (e.g. clopidogrel) are also
             eligible.

         10. History of allergy to any of the constituents of the Quadrivalent VLP Influenza
             Vaccine or a tobacco allergy;

         11. History of anaphylactic allergic reactions to plants or plants components;

         12. Any history of serious asthma (e.g. status asthmaticus, hospitalization for asthma
             control) in the last three years;

         13. Use of antihistamines 48 hours prior to study vaccination;

         14. The 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. 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-hour period is
             met;

         15. Participants who have a dermatological condition at the injection site that may
             interfere with injection site reaction rating;

         16. Participant who have received a blood transfusion within 90 days prior to study
             vaccination;

         17. Any female participant who has a positive or doubtful pregnancy test result prior to
             vaccination or who is lactating;

         18. Presence of any febrile illness (including oral temperature (OT) ≥ 38.0 ˚C within 24
             hours prior to vaccination). Such participants may be re-evaluated for enrolment after
             resolution of illness;

         19. Cancer or treatment for cancer within three years of study vaccine administration.
             Participants with a history of cancer who are disease-free without treatment for three
             years or more are eligible. Individuals with treated and uncomplicated basal cell
             carcinoma of the skin or with non-treated, non-disseminated local prostate cancer are
             eligible;

         20. 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.
             Immediate family members of the Investigator or employees of a clinical site can
             participate in the study at another clinical site, as long as the Investigator or
             employees are not involved in the study at that site;

         21. Participant with a history of Guillain-Barré syndrome.