A phase II trial multicenter, observer-blind, randomized, dose-ranging, placebo-controlled study to evaluate the immunogenicity, safety, and tolerability of a single intramuscular injection of plant-derived Seasonal VLP Quadrivalent Influenza Vaccine administered to healthy adults 18-49 years of age. A total of three hundred subjects will be randomized in four (4) groups of 75 subjects to receive one injection of either a low, a medium, or a high dose level of the quadrivalent VLP influenza vaccine or the placebo preparation (100 millimolar (mM) phosphate buffer + 150 mM sodium chloride (NaCl) + 0.01% Tween 80).
This study will be a dose escalation, cohort staggering (slow enrollment) for the 3 dose levels (low, medium or high dose level) with a placebo-controlled group: * Cohort 1: A first cohort of one hundred nineteen subjects (119) will be randomized; of these, seventy five (75) will be dosed with the lowest dose of the quadrivalent VLP vaccine, nineteen (19) will be dosed with the medium dose of the quadrivalent VLP vaccine, and twenty five (25) will receive a placebo. The 7-day safety data after the immunization will be collected and reviewed by the Data and Safety Monitoring Board (DSMB) consisting of the Principal Investigator (PI), the Sponsor's Medical Officer and three external medical experts as voting members, prior to permitting immunization with the cohort 2. * Cohort 2: A second cohort of one hundred subjects (100) subjects will be randomized; of these, fifty six (56) will be dosed with the medium dose of the quadrivalent VLP vaccine, nineteen (19) be dosed with the high dose of the quadrivalent VLP vaccine, and twenty five (25) will receive a placebo. The 7-day safety data after the immunization will be collected and reviewed by the DSMB, prior to permitting immunization with the highest dose. * Cohort 3: A third cohort of eighty one subjects (81) subjects will be randomized; of these fifty six (56) dosed with the high dose of the quadrivalent VLP vaccine and twenty five (25) will receive a placebo. Three (3) and 21 days after immunization, key safety (Day 3) and immunogenicity (Day 21) data will be collected and analyzed. All subjects will be followed for safety until Day 201 (6-month follow up), regardless the phase of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
300
A single low dose of quadrivalent VLP vaccine
A single medium dose of quadrivalent VLP vaccine
A single high dose of quadrivalent VLP vaccine
A single dose of placebo
Broward Research Group
Hollywood, Florida, United States
Miami Research Associates
Miami, Florida, United States
Immunogenicity (against vaccine strains)
Immunogenicity will be assessed by Geometric mean titers (GMTs) of hemagglutination inhibition (HI antibody on Days 0 and 21) antibodies against the vaccine strains and assessed by measuring geometric mean fold rise, seroconversion rate and seroprotection rate. Follow up serology samples for GMTs will be collected at day 201.
Time frame: 21 days after injection
Safety
Safety and tolerability will be assessed by the rate, severity and relationship to vaccination of solicited and unsolicited adverse events post-vaccination. A 6-month follow up period will be performed.
Time frame: 21 days after injection
Immunogenicity (against vaccine strains and heterologous strains)
Immunogenicity will be assessed by Geometric mean titers (GMTs) of microneutralization (MN antibody on Days 0 and 21) antibodies against the vaccine strains and assessed by measuring Geometric mean fold rise and seroconversion rate. Cross-reactivity of antibodies induced by a single dose of the quadrivalent VLP vaccine will also be assessed and measured by HI and microneutralization (MN) antibody titers for heterologous influenza strains. This will be assessed using the measures of Geometric mean fold rise, seroconversion rate and seroprotection rate (for HI only).
Time frame: 21 days after injection
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