Safety and Immunogenicity of Three Influenza Vaccines Adults Ages 18 and Older

A Phase III, Stratified, Randomized, Double-Blind, Multicenter, NonInferiority Study to Evaluate the Safety and Immunogenicity of a Cell-based Quadrivalent Subunit Influenza Virus Vaccine and Cell-based Trivalent Subunit Influenza Virus Vaccines in Adults Ages ≥18 Years of Age

Evaluate safety and immunogenicity of three influenza vaccines in adults 18 years of age and above.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: QIVc; Biological: TIV1c; Biological: TIV2c

• Study Type: Interventional
• Enrollment (Actual): 2680
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35802
  • Arizona
    • Phoenix, Arizona, United States, 85050
  • California
    • Anaheim, California, United States, 92801
    • San Diego, California, United States, 92108
  • Florida
    • Coral Gables, Florida, United States, 33134
    • Hollywood, Florida, United States, 33024
    • Melbourne, Florida, United States, 32935
    • South Miami, Florida, United States, 33143
    • West Palm Beach, Florida, United States, 33409
  • Illinois
    • Peoria, Illinois, United States, 61602
  • Indiana
    • Mishawaka, Indiana, United States, 46545
  • Iowa
    • Council Bluffs, Iowa, United States, 51503
  • Kansas
    • Newton, Kansas, United States, 67114
    • Wichita, Kansas, United States, 67207
    • Wichita, Kansas, United States, 67205
  • Louisiana
    • Metairie, Louisiana, United States, 70006
  • Maryland
    • Rockville, Maryland, United States, 20850
  • Minnesota
    • Edina, Minnesota, United States, 55435
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
    • Omaha, Nebraska, United States, 68134
  • New York
    • Endwell, New York, United States, 13760
    • Rochester, New York, United States, 14609
  • North Carolina
    • Cary, North Carolina, United States, 27518
    • Charlotte, North Carolina, United States, 28209
    • Raleigh, North Carolina, United States, 27609
    • Wilmington, North Carolina, United States, 28401
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
  • South Carolina
    • Anderson, South Carolina, United States, 29621
    • Mt. Pleasant, South Carolina, United States, 29464
  • South Dakota
    • Dakota Dunes, South Dakota, United States, 57049
  • Texas
    • Austin, Texas, United States, 78705
    • Austin, Texas, United States, 78745
    • Dallas, Texas, United States, 75231
    • Fort Worth, Texas, United States, 76135
    • San Angelo, Texas, United States, 76904
  • Utah
    • Salt Lake City, Utah, United States, 84121
    • Salt Lake City, Utah, United States, 84109
    • Salt Lake City, Utah, United States, 84124
    • South Jordan, Utah, United States, 84095

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female ages 18 years and older.
2. Individuals who give written informed consent, who can comply with study procedures, and who are available for follow-up.

Exclusion Criteria:

1. Individuals recently vaccinated against influenza
2. Subjects with contraindications to receive influenza vaccine
3. Please contact the site for additional eligibility criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QIVc; Influenza vaccine	Biological: QIVc; Novartis Investigational Quadrivalent Vaccine
Active Comparator: TIV1c; Influenza vaccine	Biological: TIV1c; Licensed Influenza Vaccine
Active Comparator: TIV2c; Influenza vaccine	Biological: TIV2c; Novartis Investigational Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1.Geometric Mean Titres (GMT) in Subjects After Receiving One Dose of Either QIVc, TIV1c or TIV2c	Immunogenicity of QIVc to comparator TIVc (For H1N1, H3N2 and B1 strain, the comparison is between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison is between QIVc and TIV2c) was assessed in terms of GMT in subjects measured by hemagglutination inhibition (HI) assay, three weeks after vaccination with one dose of either QIVc or TIV1c and TIV2c. Non-inferiority was established if the upper bound of the two-sided 95% confidence interval (CI) for the ratio of GMTs (GMT TIV1c or TIV2c /GMT QIVc) for HI antibody does not exceed the non-inferiority margin of 1.5.	Three weeks post vaccination (Day 22)
2. Percentages of Subjects Achieving Seroconversion After One Dose of Either QIVc, TIV1c or TIV2c	Immunogenicity of QIVc to comparator TIVc (For H1N1, H3N2 and B1 strain, the comparison is between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison is between QIVc and TIV2c) was assessed in terms of percentages of subjects showing seroconversion or significant increase in HI antibody titers, three weeks (day 22) after vaccination with one dose of either QIVc,TIV1c or TIV2c Seroconversion is defined in subjects seronegative at baseline (i.e., HI titer <1:10 at Day 1) as post-vaccination HI titer ≥1:40, and defined in subjects sero-positive at baseline (i.e., HI titer ≥1:10 at Day 1) as a minimum of a 4-fold increase in post-vaccination HI titer	Three weeks post vaccination (Day 22)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3. Percentages of Subjects Achieving Seroconversion After One Dose of Either QIVc, TIV1c or TIV2c in 18 to <65 and ≥ 65 Years Age Cohorts	Immunogenicity was assessed in terms of percentages of subjects showing seroconversion or significant increase in HI antibody titers, against each vaccine strains, three weeks (day 22) after vaccination with ether QIVc, TIV1c or TIV2c Seroconversion is defined in subjects seronegative at baseline (i.e., HI titer <1:10 at Day 1) as post-vaccination HI titer ≥1:40, and defined in subjects sero-positive at baseline (i.e., HI titer ≥1:10 at Day 1) as a minimum of a 4-fold increase in post-vaccination HI titer.The CBER criterion for 18 to <65 years age group is that the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion for HI antibody should meet or exceed 40% and that for the ≥ 65 years age group should meet or exceed 30%	Three weeks post vaccination (Day 22)
4. Percentages of Subjects Achieving HI Titer ≥1:40 After One Dose of Either QIVc, TIV1c or TIV2c in 18 to <65 and ≥ 65 Years Age-cohorts	Immunogenicity was assessed in terms of percentages of subjects showing HI titer ≥1:40, three weeks (day 22) after vaccination with either QIVc, TIV1c or TIV2c The CBER criterion for 18 to <65 years age group is that the lower bound of the two-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥ 1:40 should meet or exceed 70% and that for the ≥ 65 years age group should meet or exceed 60%	Three weeks post vaccination (Day 22)
5.Geometric Mean Ratios (GMR) in Subjects After One Dose of Either QIVc, TIV1c or TIV2c in 18 to ≤60 Years and ≥ 61 Years Age Cohorts	Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of post-vaccination to pre-vaccination HI GMTs, three weeks (day 22) after vaccination with either QIVc, TIV1c or TIV2c Committee for Medicinal Products for Human Use (CHMP) criterion for 18 to ≤60 years age group is >2.5 and that for ≥ 61 years age group is >2.0	Three weeks post vaccination (Day 22)
6. Percentages of Subjects Achieving Seroconversion After One Dose of Either QIVc, TIV1c or TIV2c in 18 to ≤60 Years and ≥ 61 Years Age Cohorts	Immunogenicity was assessed in terms of percentages of subjects showing seroconversion or significant increase in HI antibody titers, three weeks (day 22) after vaccination with either QIVc, TIV1c or TIV2c Seroconversion is defined in subjects seronegative at baseline (i.e., HI titer <1:10 at Day 1) as post-vaccination HI titer ≥1:40, and defined in subjects sero-positive at baseline (i.e., HI titer ≥1:10 at Day 1) as a minimum of a 4-fold increase in post-vaccination HI titer The CHMP criterion for 18 to ≤60 years age group is that the percentage of subjects achieving seroconversion or significant increase in HI titer is >40% and that for ≥ 61 years age group is >30%	Three weeks post vaccination (Day 22)
7. Percentages of Subjects Achieving HI Titer ≥1:40 After One Dose of Either QIVc, TIV1c or TIV2c in 18 to ≤60 Years and ≥ 61 Years Age Cohorts	Immunogenicity was assessed in terms of percentages of subjects showing HI titer ≥1:40, three weeks (day 22) after vaccination with either QIVc, TIV1c and TIV2c The CHMP criterion for 18 to ≤60 years age group is that the percentage of subjects achieving an HI titer ≥1:40 is >70% and that for ≥ 61 years age group is >60%	Three weeks post vaccination (Day 22)
8.Geometric Mean Titres (GMT) in Subjects After Receiving One Dose of Either QIVc, TIV1c Against B2 Strain	Immunogenicity of QIVc to TIV1c was assessed by GMT in subjects measured by HI assay, three weeks after vaccination with one dose of either QIVc or TIV1c. Superiority was established if the upper bound of the two-sided 95% CI for the ratio of GMTs (GMT TIV1c /GMT QIVc) for HI antibody does not exceed the superiority margin of 1.	Three weeks post vaccination (Day 22)
9.Percentages of Subjects Achieving Seroconversion After One Dose of Either QIVc, TIV1c Against B2 Strain	Immunogenicity of QIVc to TIV1c was assessed in terms of percentages of subjects showing seroconversion or significant increase in HI antibody titers, against influenza strain B2, three weeks (day 22) after vaccination with QIVc or TIV1c Superiority was established if the upper bound of the two-sided 95% CI for the difference between seroconversion rates (% seroconversion TIV1c - % seroconversion QIVc) for HI antibody in ≥ 18 years age group does not exceed the margin of 0 points	Three weeks post vaccination (Day 22)
10.GMT in Subjects After Receiving One Dose of Either QIVc, TIV2c Against B1 Strain	Immunogenicity of QIVc to TIV2c was assessed by GMT in subjects measured by HI assay, three weeks after vaccination with one dose of either QIVc or TIV2c. Superiority was established if the upper bound of the two-sided 95% CI for the ratio of GMTs (GMT TIV2c /GMT QIVc) for HI antibody does not exceed the superiority margin of 1	Three weeks post vaccination (Day 22)
11.Percentages of Subjects Achieving Seroconversion After One Dose of Either QIVc, TIV2c Against B1 Strain	Immunogenicity of QIVc to TIV2c in terms of percentages of subjects showing seroconversion or significant increase in HI antibody titers, against influenza strain B1, three weeks (day 22) after vaccination with QIVc or TIV2c Superiority was established if the upper bound of the two-sided 95% CI for the difference between seroconversion rates (% seroconversion TIV2c - % seroconversion QIVc) for HI antibody in ≥ 18 years age group does not exceed the margin of 0 points	Three weeks post vaccination (Day 22)
12.Number of Subjects Reporting Solicited Adverse Events (AEs) After One Dose of Either QIVc, TIV1c or TIV2c by Overall Age Group	Safety was assessed in terms of number (%) of subjects reporting solicited local and systemic reactions, day 1 to 7 after vaccination with one dose of either four (4) strain inactivated quadrivalent cell based influenza vaccine (QIVc) or trivalent inactivated influenza vaccine (TIV1c or TIV2c)	Day 1 to 7 post vaccination
13.Number of Subjects Reporting Unsolicited Adverse Events (AEs) After One Dose of Either QIVc, TIV1c or TIV2c by Overall Age Group	Safety was assessed in terms of number (%) of subjects reporting unsolicited AEs (day 1 to 22 after vaccination), serious adverse events (SAEs), medically attended AEs, AEs leading to withdrawal from the study, new onset of chronic diseases (NOCDs), and concomitant medications (day 1 to day 181 post vaccination) after receiving one dose of either four (4) strain inactivated quadrivalent cell based influenza vaccine (QIVc) or trivalent inactivated influenza vaccine (TIV1c or TIV2c)	Day 1 to 181 post vaccination

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: November 7, 2013
• First Submitted That Met QC Criteria: November 18, 2013
• First Posted (Estimate): November 25, 2013

Study Record Updates

• Last Update Posted (Estimate): December 10, 2015
• Last Update Submitted That Met QC Criteria: November 2, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Influenza; Adults; Influenza vaccine; Novartis
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: V130_01