A Study to Evaluate the Immunogenicity and Safety of bioCSL Quadrivalent Influenza Vaccine (QIV) in Adults Aged 18 Years and Above.
- Conditions
- Influenza, Human
- Interventions
- Biological: Trivalent Influenza Vaccine (TIV-1)Biological: Trivalent Influenza Vaccine (TIV-2)Biological: Quadrivalent Influenza Vaccine (QIV)
- Registration Number
- NCT02214225
- Lead Sponsor
- Seqirus
- Brief Summary
This is a study to assess the immune (antibody) response and safety of a bioCSL split virion, inactivated quadrivalent influenza vaccine, in comparison with a US licensed 2014/2015 trivalent influenza vaccine (bioCSL TIV-1), and a trivalent influenza vaccine containing the alternate B strain (bioCSL TIV-2), in healthy adult volunteers aged 18 years and above.
- Detailed Description
This multicenter, randomized, double-blinded study was conducted during the 2014-2015 Northern Hemisphere influenza immunization season to evaluate the non-inferior immune response of bioCSL QIV to that of bioCSL TIV-1 and bioCSL TIV-2 along with safety in healthy male and female adults aged ≥ 18 years. Each vaccinated subject had a maximum 25 day on-study period with a six month safety follow-up.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3484
- Males or non-pregnant females aged ≥ 18 years at the time of vaccination.
- Females of child-bearing potential (i.e., ovulating, pre-menopausal, not surgically sterile) must be abstinent or be willing to use a medically accepted contraceptive regimen for the duration of the On-study period. Females of child-bearing potential must return a negative urine pregnancy test result prior to vaccination with the vaccine.
- Known hypersensitivity to a previous dose of influenza vaccine or allergy to eggs, chicken protein, neomycin, polymyxin, or any components of bioCSL influenza vaccines.
- Vaccination against influenza in the previous 6 months.
- Known history of Guillain-Barré Syndrome or other demyelinating disease.
- Clinical signs of active infection and/or an oral temperature of ≥ 100.4°F (38.0°C).
- A clinically significant medical condition.
- Pregnant or lactating females.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Trivalent Influenza Vaccine (TIV-1) Trivalent Influenza Vaccine (TIV-1) The bioCSL study vaccine is a sterile, thiomersal-free suspension containing 45 mcg total hemagglutinin antigen per 0.5 mL dose (15 mcg each of the three recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season). Trivalent Influenza Vaccine (TIV-2) Trivalent Influenza Vaccine (TIV-2) The bioCSL study vaccine is a sterile, thiomersal-free suspension containing 45 mcg total hemagglutinin antigen per 0.5 mL dose (15 mcg each of the recommended influenza A (H1N1-, H3N2-like) strains and the alternate B strain for the Northern Hemisphere 2014/2015 influenza season). Quadrivalent Influenza Vaccine (QIV) Quadrivalent Influenza Vaccine (QIV) The bioCSL study vaccine is a sterile, thiomersal-free suspension containing 60 mcg total hemagglutinin antigen per 0.5 mL dose (15 mcg each of the four recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season).
- Primary Outcome Measures
Name Time Method The Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) in Subjects Aged ≥18 Years. 21 days after vaccination. SCR (defined as the percentage of subjects with either a prevaccination HI titer \< 1:10 and a postvaccination HI titer ≥ 1:40 or a prevaccination HI titer ≥ 1:10 and a 4-fold increase in postvaccination HI titer) was determined for each virus strain included in the vaccines: bioCSL TIV-1 and bioCSL TIV-2 SCRs were pooled for analysis of the A strains. The SCR difference was defined as the SCR percentage for bioCSL Pooled TIV or TIV-1 (B Yamagata) or TIV-2 (B Victoria) minus the SCR percentage for bioCSL QIV.
Postvaccination Geometric Mean Titer (GMT) (Statistical Analysis: GMT Ratios) in Subjects Aged ≥18 Years (Per Protocol Population). 21 days after vaccination. Immunogenicity was assessed by measuring HI titers to the four virus strains. Postvaccination GMTs were determined. (GMT dispersion values are based on unadjusted GMT values.) The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was then determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.
- Secondary Outcome Measures
Name Time Method The Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs). For 7 days following vaccination. The overall number of subjects experiencing at least one event of a local and systemic solicited AE, and the overall number of subjects with at least one severe (grade 3) local and systemic solicited AE.
The Frequency of Cellulitis-like Reaction and Cellulitis. For 28 days following vaccination. The number of subjects experiencing at least one episode of each event.
The Seroconversion Rate (SCR) (Statistical Analyses: Difference in SCR) for Each Virus Strain, Assessed Separately Within Each Age Group (18 to < 65 Years and ≥ 65 Years of Age) (Per Protocol Population). 21 days after vaccination. Non-inferiority of bioCSL QIV compared to bioCSL TIV-1, and to bioCSL TIV-2 was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age) through assessment of SCR differences as described for the primary endpoint.
Seroprotection Rates Prevaccination and Postvaccination. 21 days after vaccination. The immunogenicity of bioCSL QIV, bioCSL TIV-1 and bioCSL TIV-2 was assessed in terms of percentage of subjects with a HI titer ≥40 (seroprotection rates) prevaccination (Day 1) and postvaccination (Day 21), in age cohorts (per protocol population).
The Frequency of Serious Adverse Events (SAEs) for 6 Months Following Vaccination. For 6 months following vaccination. The number of participants reporting Serious Adverse Events for 6 months following vaccination.
Postvaccination GMT (Statistical Analyses: GMT Ratios) Assessed Separately Within Each Age Group (18 Through 64 Years and ≥ 65 Years of Age) (Per-Protocol Population). 21 days after vaccination. Immunogenicity was assessed by measuring HI titers to the four virus strains. Postvaccination GMTs were determined. (GMT dispersion values are based on unadjusted GMT values.) The GMT ratio (defined as the geometric mean of postvaccination (day 21) HI titer for TIV divided by the geometric mean of the postvaccination HI titer for QIV) for each virus strain included in the vaccines was then determined: bioCSL TIV-1 and bioCSL TIV-2 GMTs were pooled for analysis of the A strains.
Non-inferiority of bioCSL QIV compared to bioCSL TIV-1, and to bioCSL TIV-2 was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age) through assessment of GMT ratios as described for the primary endpoint.Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by the GMT (Statistical Analysis: GMT Ratio) for This Strain, Overall and by Age Cohort (Per Protocol Population). 21 days after vaccination. Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. The GMT ratio was calculated as bioCSL QIV GMT/bioCSL TIV GMT for the superiority analyses, which is the reverse of how it was calculated for the non-inferiority analyses.
(GMT dispersion values are based on unadjusted GMT values.)Immunologic Superiority of the Alternate B Strain in bioCSL QIV, as Determined by Seroconversion Rate (SCR) (Statistical Analysis: Difference in SCR) for This Strain, Overall and by Age Cohort (Per Protocol Population) 21 days after vaccination. Immunologic superiority of the alternate B strain (ie, the influenza B strain included in the QIV but not in the TIV formulation) in bioCSL QIV was assessed separately within each age group (18 to \< 65 years and ≥ 65 years of age), and overall. The SCR difference was calculated as bioCSL QIV SCR minus bioCSL TIV SCR, which is the reverse of how it was calculated for the non-inferiority analyses. For the SCR comparison superiority was demonstrated if the lower limit of the two-sided 95% CI of the difference of the seroconversion rates was greater than 0 for each B strain in QIV compared with the corresponding B strain not contained in each TIV.
The Frequency and Severity of Unsolicited AEs. For 28 days following vaccination. The overall number of subjects experiencing at least one event of an unsolicited AE, and the overall number of subjects with at least one severe (grade 3) unsolicited AE.
Geometric Mean of HI Titers (GMTs) Prevaccination and Postvaccination. 21 days after vaccination. The immunogenicity of bioCSL QIV, bioCSL TIV-1 and bioCSL TIV-2 was assessed in terms of geometric mean HI titers (GMT) prevaccination (Day 1) and postvaccination (Day 21), in age cohorts (per protocol population).
Geometric Mean Fold Titer Change From Prevaccination to Postvaccination. 21 days after vaccination. The immunogenicity of bioCSL QIV, bioCSL TIV-1 and bioCSL TIV-2 assessed in terms of Geometric Mean Fold Increase (GMFI, defined as the geometric mean of the fold increases of postvaccination antibody titer over the prevaccination antibody titer) by Age Cohort (Per Protocol Population).
Seroconversion Rates 21 days after vaccination. The immunogenicity of bioCSL QIV, bioCSL TIV-1 and bio CSL TIV-2 was assessed in terms of the seroconversion rate, ie, percentage of subjects with either a prevaccination HI titer \< 1:10 and a postvaccination HI titer ≥ 1:40, or a prevaccination titer ≥ 1:10 and a ≥ 4-fold increase in post-vaccination titer. Data presented in age cohorts (per protocol population).
Trial Locations
- Locations (33)
Site 296
🇺🇸Huntsville, Alabama, United States
Site 286
🇺🇸Los Angeles, California, United States
Site 315
🇺🇸San Diego, California, United States
Site 301
🇺🇸Milford, Connecticut, United States
Site 293
🇺🇸Melbourne, Florida, United States
Site 297
🇺🇸Jacksonville, Florida, United States
Site 292
🇺🇸Savannah, Georgia, United States
Site 289
🇺🇸Meridian, Idaho, United States
Site 294
🇺🇸Peoria, Illinois, United States
Site 295
🇺🇸Mishawaka, Indiana, United States
Site 317
🇺🇸Witchita, Kansas, United States
Site 310
🇺🇸Methuen, Massachusetts, United States
Site 291
🇺🇸Rockville, Maryland, United States
Site 287
🇺🇸Saint Louis, Missouri, United States
Site 316
🇺🇸Bellevue, Nebraska, United States
Site 298
🇺🇸Las Vegas, Nevada, United States
Site 313
🇺🇸Rochester, New York, United States
Site 285
🇺🇸Binghamton, New York, United States
Site 306
🇺🇸Raleigh, North Carolina, United States
Site 302
🇺🇸Charlotte, North Carolina, United States
Site 309
🇺🇸Wilmington, North Carolina, United States
Site 299
🇺🇸Oklahoma City, Oklahoma, United States
Site 305
🇺🇸Winston-Salem, North Carolina, United States
Site 307
🇺🇸Mount Pleasant, South Carolina, United States
Site 311
🇺🇸Jefferson City, Tennessee, United States
Site 308
🇺🇸Bristol, Tennessee, United States
Site 312
🇺🇸Knoxville, Tennessee, United States
Site 304
🇺🇸Knoxville, Tennessee, United States
Site 288
🇺🇸San Angelo, Texas, United States
Site 283
🇺🇸Austin, Texas, United States
Site 300
🇺🇸Salt Lake City, Utah, United States
Site 282
🇺🇸Forth Worth, Texas, United States
Site 303
🇺🇸Charlottesville, Virginia, United States