A Phase 3, Randomized, Observer-Blind, Controlled, Multicenter, Clinical Study to Evaluate Immunogenicity and Safety of a MF59-Adjuvanted Quadrivalent Subunit Cell-derived Influenza Vaccine (aQIVc) in Comparison With Quadrivalent Influenza Vaccines, in Adults Aged 50 Years and Older.
Overview
- Phase
- Phase 3
- Intervention
- Investigational aQIVc
- Conditions
- Influenza, Human
- Sponsor
- Seqirus
- Enrollment
- 7741
- Locations
- 95
- Primary Endpoint
- Immunogenicity Endpoint: Humoral immune responses of 3 lots of aQIVc compared in pairs in terms of Day 29 GMT ratio between each pair among the 3 lots, from antibody titers measured via HI assay.
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 3, randomized, parallel-group, comparator-controlled, observer-blind, multicenter study of immunogenicity and safety in approximately 7700 male and female adults aged 50 years and older (approximately equally split between two age groups: 50-64 years; 65 years and older), who are healthy or have stable comorbidities that increase their risk of complications from influenza infection. Three lots of aQIVc will be evaluated for consistency and pooled for the comparison with the 2 control vaccines.
Subjects will be randomly assigned to receive 1 of 3 lots of aQIVc, QIVr, or aQIV in a 1:1:1:2:2 ratio (for a 3:2:2 ratio for aQIVc, QIVr, and aQIV).
The study will have a treatment period (Day 1 to Day 29) and a follow-up period (Day 30 up to Day 181); a subset of 770 subjects will be followed up up to Day 365.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Individuals, aged 50 years and older, who are healthy or have stable comorbidities that increase their risk of complications from influenza infection
- •Individuals who can comply with all study procedures
Exclusion Criteria
- •Progressive, unstable, or uncontrolled clinical conditions
- •Known hypersensitivity or allergy to any study vaccine component
- •Known history of Guillain-Barré syndrome or other demyelinating disease
- •Condition representing a contraindication to vaccination or blood draw
- •Abnormal function of immune system due to known disorder or medication.
- •Influenza vaccination within 180 days prior to informed consent.
Arms & Interventions
Investigational aQIVc group
Intervention: Investigational aQIVc
licensed QIVr group
Intervention: licensed QIVr
licensed aQIV group
Intervention: licensed aQIV
Outcomes
Primary Outcomes
Immunogenicity Endpoint: Humoral immune responses of 3 lots of aQIVc compared in pairs in terms of Day 29 GMT ratio between each pair among the 3 lots, from antibody titers measured via HI assay.
Time Frame: Day 29
HI assay will be measured using cell-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains.
Immunogenicity Endpoint: Humoral immune responses of aQIVc in comparison with QIVr and aQIV vaccines in terms of Day 29 GMT and GMT ratio of antibodies measured via HI assay.
Time Frame: Day 29
HI assay will be measured using cell-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains. Noninferiority of aQIVc versus comparator (QIVr or aQIV) will be demonstrated if the lower limit (LL) of the 2-sided 97.5% CI for the Day 29 GMT ratio (aQIVc/comparator) is ≥0.67 for each of the 4 vaccine strains.
Immunogenicity Endpoint: Humoral immune responses of aQIVc in comparison with QIVr and aQIV vaccines in terms of Day 1 to Day 29 SCR and SCR difference, from antibody titers measured via HI assay.
Time Frame: Day 1 and Day 29
HI assay will be measured using cell-derived target viruses for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains. SCR is the percentage of subjects with seroconversion (defined as either a prevaccination \[Day 1\] titer \<1:10 and a postvaccination \[Day 29\] titer ≥1:40, or a prevaccination titer ≥1:10 and a ≥4-fold increase in postvaccination titer). Noninferiority of aQIVc versus comparator (QIVr or aQIV) will be demonstrated if the lower limit (LL) of the 2-sided 97.5% CI for the difference in SCR (aQIVc minus comparator) is ≥-10% for each of the 4 vaccine strains.
Secondary Outcomes
- Immunogenicity Endpoint: Humoral immune responses of aQIVc in comparison with aQIV vaccine in terms of Day 29 SCR and SCR difference, GMT and GMT ratio of antibodies measured via HI assay in subjects 65 years and older.(Day 1 and Day 29)
- Immunogenicity Endpoint: Humoral immune responses of aQIVc in comparison with QIVr and aQIV vaccines in terms of Day 29 GMT and GMT ratio of antibodies measured via HI assay.(Day 29)
- Immunogenicity Endpoints: For aQIVc, QIVr, and aQIV vaccines, Day 29 GMT, Day 1 to Day 29 GMFI, Percentage of subjects with HI titer ≥1:40 at Day 29, Day 1 to Day 29 SCR, SCR differences and GMT ratio of antibodies measured via HI assay.(Day 1 and Day 29)
- Immunogenicity Endpoints: For aQIVc and aQIV vaccines, Day 29 GMT, Day 1 to Day 29 GMFI, Percentage of subjects with HI titer ≥1:40 at Day 29, Day 1 to Day 29 SCR, SCR differences, and GMT ratio of antibodies measured via HI assay.(Day 1 and Day 29)
- Immunogenicity Endpoints: For aQIVc, QIVr and aQIV vaccines, GMT, GMFI, Percentage of subjects with HI titer ≥1:40, SCR, SCR differences, and GMT ratio of antibodies measured via HI assay.(Day 1 up to Day 365)
- Immunogenicity Endpoints: For aQIVc, QIVr and aQIV vaccines, GMT, GMFI, SCR, SCR difference, and GMT ratio of antibodies measured via MN assay.(Day 1 up to Day 365)
- Safety endpoints: For aQIVc, QIVr and aQIV vaccines, the percentages of Subjects with Solicited Local Adverse Events, Solicited Systemic Adverse Events, and Severe Solicited Local and/or Systemic AEs.(Day 1 to Day 7)
- Safety endpoints: For aQIVc, QIVr and aQIV vaccines, the percentage of Subjects with Unsolicited Adverse Events.(Day 1 to Day 29)
- Safety endpoints: For aQIVc, QIVr and aQIV vaccines, the percentages of subjects with Serious Adverse Events (SAEs), AEs Leading to Withdrawal, Adverse Events of Special Interest (AESI) and non-serious Medically Attended Adverse Events (MAAEs).(Day 1 to Day 365)