Clinical Study to Evaluate the Safety, Immunogenicity and Efficacy of Investigational Flu Vaccine Compared to Approved Flu Vaccine in Children.

A Phase III, Stratified, Randomized, Observer Blind, Controlled, Multicenter Clinical Study to Evaluate the Safety, Immunogenicity and Efficacy of an Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine Compared to Non-Adjuvanted Comparator Influenza Vaccine in Children ≥6 to < 72 Months of Age.

Safety, Immunogenicity and Efficacy of an Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine Compared to Non-Adjuvanted Comparator Influenza Vaccine in Children ≥6 to <72 Months of Age. The study was conducted during the 2013/2014 and 2014/2015 northern hemisphere influenza season.

Study Overview

• Status: Completed
• Conditions: Influenza Virus
• Intervention / Treatment: Biological: Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine (aQIV); Biological: Non-adjuvanted Trivalent Influenza Vaccine (TIV) / Quadrivalent Influenza Vaccine (QIV)

• Study Type: Interventional
• Enrollment (Actual): 10644
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada
    • 186, Novartis Investigational Site
  • Québec, Canada, G1E 7G9
    • 183, Novartis Investigational Site
  • Ontario
    • Newmarket, Ontario, Canada, L3Y 5G8
      • 180, Novartis Investigational Site
    • Sudbury, Ontario, Canada, P3E 1H5
      • 184, Novartis Investigational Site
    • Toronto, Ontario, Canada, M9V 4B4
      • 182,Novartis Investigational Site
• Finland
  • Espoo, Finland, FI-02230
    • 001, Novartis Investigational Site
  • Helsinki, Finland, FIN-00100
    • 003, Novartis Investigational Site
  • Helsinki, Finland, FIN-00930
    • 002, Novartis Investigational Site
  • Järvenpää, Finland, FIN-04400
    • 004, Novartis Investigational Site
  • Kokkola, Finland, FI-67100
    • 005, Novartis Investigational Site
  • Oulu, Finland, 90220
    • 006, Novartis Investigational Site
  • Pori, Finland, FI-28100
    • 007, Novartis Investigational Site
  • Seinäjoki, Finland, FI-60100
    • 008, Novartis Investigational Site
  • Tampere, Finland, FIN-33100
    • 009, Novartis Investigational Site
  • Turku, Finland, FIN-20520
    • 010, Novartis Investigational Site
  • Vantaa, Finland, FIN-01300
    • 011, Novartis Investigational Site
• Italy
  • Florence, Italy, 50139
    • 030, Novartis Investigational Site
  • Genova, Italy, 16132
    • 023, Novartis Investigational Site
  • Milano, Italy, 20122
    • 020, Novartis Investigational Site
  • Milano, Italy, 20157
    • 026, Novartis Investigational Site
  • Napoli, Italy, 80131
    • 025, Novartis Investigational Site
  • Novara, Italy, 28100
    • 021, Novartis Investigational Site
  • Padova, Italy, 35128
    • 022, Novartis Investigational Site
  • Pisa, Italy, 56126
    • 024, Novartis Investigational Site
  • Sassari, Italy, 07100
    • 028, Novartis Investigational Site
• Mexico
  • Durango, Mexico, 34000
    • 176, Novartis Investigational Site
  • Mexico, Mexico, 04530
    • 170, Novartis Investigational Site
  • Mexico, Mexico, 06760
    • 177, Novartis Investigational Site
  • Mexico, Mexico, 14000
    • 178, Novartis Investigational Site
  • Mexico, Mexico, 7020
    • 175, Novartis Investigational Site
  • Michoacan
    • Morelia, Michoacan, Mexico, 58070
      • 173, Novartis Investigational Site
• Philippines
  • Manila, Philippines, 1000
    • 302, Novartis Investigational Site
  • Manila, Philippines, 1001
    • 301, Novartis Investigational Site
  • Muntinlupa, Philippines, 1781
    • 303, Novartis Investigational Site
  • Muntinlupa, Philippines, 1781
    • 304, Novartis Investigational Site
  • Muntinlupa, Philippines, 1781
    • 305, Novartis Investigational Site
  • Cavite
    • Dasmariñas, Cavite, Philippines, 4114
      • 300, Novartis Investigational Site
  • Muntilupa
    • Alabang, Muntilupa, Philippines, 1781
      • 306, Novartis Investigational Site
• Poland
  • Debica, Poland, 39-200
    • 040, Novartis Investigational Site
  • Katowice, Poland, 40-018
    • 042, Novartis Investigational Site
  • Leczna, Poland, 21-010
    • 052, Novartis Investigational Site
  • Lodz, Poland, 91347
    • 048, Novartis Investigational Site
  • Lubartow, Poland, 21-100
    • 049, Novartis Investigational Site
  • Oborniki Slaskie, Poland, 55-120
    • 051, Novartis Investigational Site
  • Osielsko, Poland, 86-031
    • 046, Novartis Investigational Site
  • Siemianowice Slaskie, Poland, 41-103
    • 043, Novartis Investigational Site
  • Tarnow, Poland, 33-100
    • 047, Novartis Investigational Site
  • Warszawa, Poland, 01809
    • 041, Novartis Investigational Site
  • Warszawa, Poland, 04-730
    • 050, Novartis Investigational Site
  • Wola, Poland, 43-225
    • 045, Novartis Investigational Site
  • Wroclaw, Poland, 51215
    • 044, Novartis Investigational Site
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • 257, Novartis Investigational Site
  • San Juan, Puerto Rico, 00909
    • 415, Novartis Investigational vaccine
  • San Juan, Puerto Rico, 00921
    • 415, Novartis Investigational Site
• Spain
  • Granada, Spain, 18009
    • 074, Novartis Investigational Site
  • Madrid, Spain, 28041
    • 076, Novartis Investigational Site
  • Madrid, Spain, 28046
    • 077, Novartis Investigational Site
  • Malaga, Spain, 29011
    • 79, Novartis Investigational Site
  • Valencia, Spain, 46026
    • 078, Novartis Investigational Site
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • 80, Novartis Investigational Site
  • Galicia
    • Santiago, Galicia, Spain, 15701
      • 075, Novartis Investigational Site
• Taiwan
  • Taichung, Taiwan, 40447
    • 344, Novartis Investigational Site
  • Taichung, Taiwan, 40705
    • 345, Novartis Investigational Site
  • Taipei City, Taiwan, 10041
    • 340, Novartis Investigational Site
  • Taipei City, Taiwan, 10449
    • 341, Novartis Investigational Site
  • Taoyuan, Taiwan, 333
    • 342, Novartis Investigational Site
  • New Taipei City
    • Banciao, New Taipei City, Taiwan, 220
      • 343, Novartis Investigational Site
  • Taipei City
    • Datong, Taipei City, Taiwan, 10341
      • 346, Novartis Investigational Site
• Thailand
  • Bangkok, Thailand, 10400
    • 320, Novartis Investigational Site
  • Bangkok, Thailand, 10400
    • 324, Novartis Investigational Site
  • Bangkok
    • Bangkoknoi, Bangkok, Thailand, 10700
      • 321, Novartis Investigational Site
    • Bangkoknoi, Bangkok, Thailand, 10700
      • 322, Novartis Investigational Site
    • Pathum Wan, Bangkok, Thailand, 10330
      • 323, Novartis Investigational Site
    • Ratchathewi, Bangkok, Thailand, 10400
      • 327, Novartis Investigational Site
  • Prathumthani
    • Pathum Thani, Prathumthani, Thailand, 12120
      • 325, Novartis Investigational Site
  • Songkhia
    • Hat Yai, Songkhia, Thailand, 90110
      • 326, Novartis Investigational Site
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • 222, Novartis Investigational Site
  • Arkansas
    • Harrisburg, Arkansas, United States, 72432
      • 267, Novartis Investigational Site
  • California
    • Anaheim, California, United States, 92801
      • 259, Novartis Investigational Site
    • Anaheim, California, United States, 92804
      • 280, Novartis Investigational Site
    • Baldwin Park, California, United States, 91706
      • 213, Novartis Investigational Site
    • Downey, California, United States, 90241
      • 407, Novartis Investigational Site
    • La Puente, California, United States, 91774
      • 238, Novartis Investigational Site
    • Ontario, California, United States, 91762
      • 411, Novartis Investigational Site
    • Paramount, California, United States, 90723
      • 202, Novartis Investigational Site
    • San Diego, California, United States, 92103
      • 250, Novartis Investigational Site
    • San Francisco, California, United States, 94102
      • 293, Novartis Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80902
      • 243, Novartis Investigational Site
    • Denver, Colorado, United States, 80902
      • 249, Novartis Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33432
      • 229, Novartis Investigational Site
    • Hialeah, Florida, United States, 33013
      • 416, Novartis Investigational Site
    • Hialeah, Florida, United States, 33106
      • 287, Novartis Investigational Site
    • Homestead, Florida, United States, 34239
      • 412, Novartis Investigational Site
    • Melbourne, Florida, United States, 32935
      • 224, Novartis Investigational Site
    • Miami, Florida, United States, 33015
      • 417, Novartis Investigational Site
    • Miami, Florida, United States, 33144
      • 404, Novartis Investigational Site
    • Miami, Florida, United States, 33172
      • 285, Novartis Investigational Site
    • Miami, Florida, United States, 33412
      • 277,Novartis Investigational Site
    • Opa-locka, Florida, United States, 33054
      • 234, Novartis Investigational Site
    • Orlando, Florida, United States, 32801
      • 297, Novartis Investigational Site
    • Orlando, Florida, United States, 32806
      • 297, Novartis Investigational vaccine
    • Sarasota, Florida, United States, 34239
      • 410, Novartis Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • 401, Novartis iNvestiagtional Site
  • Illinois
    • DeKalb, Illinois, United States, 60115
      • 299, Novartis Investigational Site
    • Peoria, Illinois, United States, 61602
      • 268, Novartis Investigational Site
  • Kansas
    • Augusta, Kansas, United States, 67010
      • 209, Novartis Investigational Site
    • Newton, Kansas, United States, 67114
      • 210, Novartis Investigational Site
    • Park City, Kansas, United States, 67219
      • 274 Novartis Investigational Site
    • Wichita, Kansas, United States, 67205
      • 211, Novartis Investigational Site
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • 269, Novartis Investigational Site
    • Louisville, Kentucky, United States, 40202
      • 226, Novartis Investigational Site
    • Louisville, Kentucky, United States, 40217
      • 248, Novartis Investigational Site
    • Louisville, Kentucky, United States, 40291
      • 207, Novartis Investigational Site
    • Louisville, Kentucky, United States, 40291
      • 290, Novartis Investigational Site
  • Louisiana
    • Haughton, Louisiana, United States, 71037
      • 265, Novartis Investigational Site
    • Mangham, Louisiana, United States, 71259
      • 408, Novartis Investigational Site
    • Metairie, Louisiana, United States, 70006
      • 225, Novartis Investigational Site
    • Metairie, Louisiana, United States, 70006
      • 233, Novartis Investigational Site
    • Monroe, Louisiana, United States, 71201
      • 418, Novartis Investigational SIte
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • 262, Novartis Investigational site
    • Frederick, Maryland, United States, 21702
      • 263, Novartis Investigational Site
    • Silver Spring, Maryland, United States, 20910
      • 405, Novartis Investigational Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55108
      • 278, Novartis Investigational Site
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • 221, Novartis Investigational Site
    • Fremont, Nebraska, United States, 68025
      • 219, Novartis Investigational Site
    • Omaha, Nebraska, United States, 68114
      • 402, Novartis Investigational Site
    • Omaha, Nebraska, United States, 68131
      • 288, Novartis Investigational Site
    • Omaha, Nebraska, United States, 68134
      • 228, Novartis Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89014
      • 244, Novartis Investigational Site
    • Las Vegas, Nevada, United States, 89106
      • 286, Novartis Investigational site
  • New York
    • Binghamton, New York, United States, 13901
      • 255, Novartis Investigational Site
    • Brooklyn, New York, United States, 11201
      • 414, Novartis Investigational Site
    • Syracuse, New York, United States, 13057
      • 264, Novartis Investigational Site
  • North Carolina
    • Boone, North Carolina, United States, 28607
      • 409, Novartis Investigational Site
    • Cary, North Carolina, United States, 27518
      • 266, Novartis Investigational Site
    • Clyde, North Carolina, United States, 28721
      • 403, Novartis Investigational Site
  • Ohio
    • Akron, Ohio, United States, 44311
      • 240, Novartis Investigational Site
    • Cleveland, Ohio, United States, 44122
      • 254, Novartis Investigational Site
    • Dayton, Ohio, United States, 45406
      • 245, Novartis Investigational Site
    • Dayton, Ohio, United States, 45409
      • 281, Novartis Investigational Site
    • Dayton, Ohio, United States, 45409
      • 281, Novartis Investigational vaccines
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74127
      • 256, Novartis Investigational Site
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16505
      • 292, Novartis Investigational Site
    • Scottdale, Pennsylvania, United States, 15683
      • 270, Novartis Investigational Site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • 220, Novartis Investigational Site
    • Barnwell, South Carolina, United States, 29812
      • 406, novartis Investigational Site
    • Charleston, South Carolina, United States, 29407
      • 272, Novartis Investigational Site
    • Moncks Corner, South Carolina, United States, 29461
      • 232, Novartis Investigational Site
    • Spartanburg, South Carolina, United States, 27262
      • 291, Novartis Investigational vaccine
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • 283, Novartis Investigational Site
  • Texas
    • Austin, Texas, United States, 78705
      • 208, Novartis Investigational Site
    • Fort Worth, Texas, United States, 76107
      • 247, Novartis Investigational Site
    • Fort Worth, Texas, United States, 76135
      • 217, Novartis Investigational Site
    • San Angelo, Texas, United States, 76904
      • 214, Novartis Investigational Site
    • San Antonio, Texas, United States, 78229
      • 400, Novartis investigational Site
    • Tomball, Texas, United States, 77375
      • 260, Novartis Investigational Site
  • Utah
    • Layton, Utah, United States, 84041
      • 295, Novartis Investigational Site
    • Salt Lake City, Utah, United States, 84109
      • 236, Novartis Investigational Site
    • Salt Lake City, Utah, United States, 84121
      • 212, Novartis Investigational Site
    • Salt Lake City, Utah, United States, 84124
      • 246, Novartis Investigational Site
    • Spanish Fork, Utah, United States, 84660
      • 279, Novartis Investigational Site
    • Syracuse, Utah, United States, 84075
      • 282, Novartis Investigational Site
    • West Haven, Utah, United States, 84401
      • 294, Novartis Investigational Site
    • West Jordan, Utah, United States, 84088
      • 201, Novartis Investigational Site
    • West Jordan, Utah, United States, 84088
      • 271, Novartis Investigational Site
  • Virginia
    • Burke, Virginia, United States, 22015
      • 251, Novartis Investigational Site
    • Vienna, Virginia, United States, 22180
      • 296, Novartis Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 5 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children, males and females, healthy or at high risk of complications from influenza, between ≥6 months to <72 months of age
• Documented consent provided by the subject's parent(s)/legal guardian(s)
• Subjects and/or subject's parent(s)/legal guardian(s) able to comply with all study procedures.

Exclusion Criteria:

• Children with history of allergy to vaccine components.
• Additional eligibility criteria may be discussed by contacting the site

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: aQIV; flu vaccine	Biological: Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine (aQIV); 1 or 2 doses (naïve / non-naive subjects) 0.25 ml: ≥6 months to <36 months, 0.5 ml: ≥36 months to <72 months
Active Comparator: non-adjuvanted comparator; flu vaccine	Biological: Non-adjuvanted Trivalent Influenza Vaccine (TIV) / Quadrivalent Influenza Vaccine (QIV); 1 or 2 doses (naïve / non-naive subjects) 0.25 ml: ≥6 months to <36 months, 0.5 ml: ≥36 months to <72 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Endpoint: First-Occurrence Reverse Transcription-Polymerase Chain Reaction (RT-PCR) Confirmed Influenza A and/or B of Any Influenza Strain in Subjects ≥6 to <72 Months of Age	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was determined by the number of subjects ≥6 to <72 months of age with RT-PCR confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥21 days and ≤180 days after the last vaccination or until the end of the influenza season, whichever was longer. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).	≥21 days and ≤180 days after the last vaccination or until the end of the influenza season (Northern Hemisphere: end of June; Southern Hemisphere: end of December; Philippines/Thailand: end of October), whichever was longer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Endpoint: First-Occurrence RT-PCR Confirmed Influenza A and/or B of Any Influenza Strain in Subjects ≥6 to <24 Months, ≥6 to <36 Months and ≥36 to <72 Months of Age.	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was determined by the number of subjects with RT-PCR confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥21 days and ≤180 days after the last vaccination or until the end of the influenza season, whichever was longer. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).	≥21 days and ≤180 days after the last vaccination or until the end of the influenza season (Northern Hemisphere: end of June; Southern Hemisphere: end of December; Philippines/Thailand: end of October), whichever was longer
Efficacy Endpoint: First-Occurrence Culture Confirmed Influenza A and/or B of Any Influenza Strain in Subjects ≥6 to <72 Months, ≥6 to <24 Months, ≥6 to <36 Months and ≥36 to <72 Months of Age	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was determined by the number of subjects with culture confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥21 days and ≤180 days after the last vaccination or until the end of the influenza season, whichever was longer. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).	≥21 days and ≤180 days after the last vaccination or until the end of the influenza season (Northern Hemisphere: end of June; Southern Hemisphere: end of December; Philippines/Thailand: end of October), whichever was longer
Efficacy Endpoint: First-occurrence RT-PCR and Culture Confirmed Influenza A and/or B of Any Influenza Strain in Subjects at High Risk of Influenza Complications	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was determined by the number of subjects ≥6 to <72 months of age with RT-PCR confirmed and culture confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥21 days and ≤180 days after the last vaccination or until the end of the influenza season, whichever was longer, in healthy subjects and subjects at risk of influenza related complications. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).	≥21 days and ≤180 days after the last vaccination or until the end of the influenza season (Northern Hemisphere: end of June; Southern Hemisphere: end of December; Philippines/Thailand: end of October), whichever was longer
Efficacy Endpoint: First-occurrence RT-PCR and Culture Confirmed Influenza A and/or B of Any Influenza Strain in Naive and Non-naive Subjects Separately	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was determined by the number of subjects with RT-PCR confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥21 days and ≤180 days after the last vaccination or until the end of the influenza season, whichever was longer. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).	≥21 days and ≤180 days after the last vaccination or until the end of the influenza season (Northern Hemisphere: end of June; Southern Hemisphere: end of December; Philippines/Thailand: end of October), whichever was longer
Efficacy Endpoint: First-occurrence RT-PCR-confirmed Influenza A and/or B of Any Influenza Strain in Subjects ≥6 to <72 Months of Age at ≥7 Days and at ≥14 Days After First Vaccination up to the Day of Second Vaccination in Vaccine naïve Subjects Only	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was based on the number of vaccine naive subjects ≥6 to <72 months of age with RT-PCR confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥7 days and ≥14 days after the first vaccination up to the day of the second vaccination. TIV was used as the comparator in Season 1; and QIV was used as the comparator in Season 2. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).	≥7 days and at ≥14 days after first vaccination up to day of second vaccination
Efficacy Endpoint: First-occurrence RT-PCR-confirmed Influenza A and/or B of Any Influenza Strain in Subjects ≥6 to <72 Months of Age Occurring at ≥7 Days and ≤21 Days After Last Vaccination, in All Subjects.	Relative efficacy of aQIV compared to non-adjuvanted comparator (TIV/QIV) was based on the number of vaccine naïve subjects ≥6 to <72 months of age with RT-PCR confirmed occurrence of influenza A and/or B of any influenza strain that occurred at ≥7 days and ≤21 after the last vaccination. TIV was used as the comparator in Season 1; and QIV was used as the comparator in Season 2. Efficacy was determined on influenza cases caused by any of the influenza strains related to the two A subtypes and the B lineage(s) common to aQIV and TIV (i.e. A/H1N1, A/H3N2 and B/Yamagata during first influenza season), and common to aQIV and QIV (i.e. A/H1N1, A/H3N2 and both B lineages during second season and through the end of the trial).	≥7 days and ≤21 days after the last vaccination
Immunogenicity Endpoint: Hemagglutination Inhibition (HI) Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms of Geometric Mean Titers (GMTs) and GMT Ratios in Subjects ≥6 to <72 Months of Age	Pooled GMT values across both naïve and non-naïve subjects are provided for the Day 22/50 (ie, 21 days after last vaccination) and Day 181/209 (ie, 180 days after last vaccination) assessments; Nonadjuvanted TIV administered in Season 1 and nonadjuvanted QIV administered in Season 2; Homologous strains: A/H1N1=A/California/7/2009 pdm09-like virus, A/H3N2=A/Texas/50/2012, B/ Yamagata=B/Massachusetts/2/2012 and B/Victoria=B/Brisbane/60/2008; For B/Victoria results from Season 2 only are presented for both vaccine groups and used in the vaccine comparison analysis.	Baseline (Day 1), Day 29, Day 50 and Day 209 for vaccine naïve subjects; Baseline (Day 1), Day 22 and Day 181 for vaccine non-naïve subjects
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms of Geometric Mean Titers (GMTs) in Vaccine Naive Subjects ≥6 to <72 Months of Age	GMTs for vaccine naïve subjects are provided by strain for Day 29 and Day 50; Nonadjuvanted TIV administered in Season 1 and nonadjuvanted QIV administered in Season 2; Homologous strains: A/H1N1=A/California/7/2009 pdm09-like virus, A/H3N2=A/Texas/50/2012, B/ Yamagata=B/Massachusetts/2/2012 and B/Victoria=B/Brisbane/60/2008; For B/Victoria results from Season 2 only are presented for both vaccine groups and used in the vaccine comparison analysis.	Day 29 and Day 50
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms GMT and GMT Ratios at 21 Days After Last Vaccination in Healthy vs High Risk Subjects ≥6 to <72 Months of Age	HI GMT was assessed on Day 1 and Day 50 for vaccine naïve healthy vs high risk subjects; and HI GMT were assessed on Day 1 and Day 22 for vaccine non-naïve healthy vs high risk subjects; pooled GMT values across both naïve and non-naïve subjects are provided for Day 22/50 (ie, 21 days after last vaccination) assessments.	Baseline (Day 1) and 21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms of Geometric Mean Ratios (GMR) in Subjects ≥6 to <72 Months of Age	The fold-increase in HI antibodies in response to vaccination was assessed as the GMR between all post-vaccination titers (ie, Day 29, 50, 209 for vaccine naïve subjects; Day 22, 181 for vaccine non-naïve subjects) and the baseline (Day 1) titer. Assessed GMRs thus correspond to Day 29/Day 1, Day 50/Day 1, and Day 209/Day 1 for vaccine naïve subjects and Day 22/Day 1 and Day 181/Day 1 for vaccine non-naïve subjects. Pooled GMR values across both naïve and non-naïve subjects are provided for Day (22/50)/Day 1 (ie, 21 days after last vaccination) and Day (181/209)/Day 1 (ie, 180 days after last vaccination); Nonadjuvanted TIV administered in Season 1 and nonadjuvanted QIV administered in Season 2; Homologous strains: A/H1N1=A/California/7/2009 pdm09-like virus, A/H3N2=A/Texas/50/2012, B/Yamagata=B/Massachusetts/2/2012 and B/Victoria=B/Brisbane/60/2008; For B/Victoria results from Season 2 only are presented for both vaccine groups and used in the vaccine comparison analysis.	Baseline (Day 1), Day 29, Day 50 and Day 209 for vaccine naïve subjects; Baseline (Day 1), Day 22 and Day 181 for vaccine non-naïve subjects
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms of Seroconversion (SC) Rates and Difference in SC Rates at 21 Days in Subjects ≥6 to <72 Months of Age	SC rates were assessed on Day 1 and Day 50 (ie, 21 days after two vaccinations) for vaccine naïve subjects; and on Day 1 and Day 22 (ie, 21 days after one vaccination) for vaccine non-naïve subjects; values pooled across naive and non-naive subjects are provided. Seroconversion is defined as HI ≥ 1:40 for subjects negative at baseline (ie, HI titer<1:10); or a minimum 4-fold increase in HI titer for subjects positive at baseline (ie, HI titer ≥ 1:10); Nonadjuvanted TIV administered in Season 1 and nonadjuvanted QIV administered in Season 2; Homologous strain: A/H1N1=A/California/7/2009 pdm09-like virus, A/H3N2=A/Texas/50/2012, B/Yamagata=B/Massachusetts/2/2012 and B/Victoria=B/Brisbane/60/2008; For B/Victoria results from Season 2 only are presented for both vaccine groups and used in the vaccine. comparison analysis (N=745 for aQIV, N=738 for comparator).	Baseline (Day 1) and 21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms of Percentage of Subjects With HI Titer ≥ 1:40 and Percentage Differences at 180 Days After Last Vaccination in Subjects ≥6 to <72 Months of Age	Antibody response was assessed as the percentage of subjects with HI titer of ≥1:40 at 180 days after last vaccination (ie, Day 209 for vaccine naïve subjects and Day 181 for vaccine non-naïve subjects). Results were then pooled across both vaccine naïve and non-naïve subjects. Homologous strains: A/H1N1=A/California/7/2009 pdm09-like virus, A/H3N2=A/Texas/50/2012, B/Yamagata=B/Massachusetts/2/2012 and B/Victoria=B/Brisbane/60/2008; B/Victoria results from Season 1 and Season 2 (aQIV) and Season 2 (comparator) are presented.	Baseline (Day 1) and 180 days after the last vaccination (Day 209 for vaccine naive subjects; Day 181 for vaccine non-naïve subjects)
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Each of the Vaccine Strains in Terms of Percentage of Subjects With HI Titers ≥1:110, ≥1:151, ≥1:215, ≥1:330, and ≥1:629 in Subjects ≥6 to <72 Months of Age	Antibody response was assessed as the percentage of subjects and differences of percentage of subjects with HI titers of ≥1:110, ≥1:151, ≥1:215, ≥1:330, and ≥1:629 at 21 days after last vaccination (ie, Day 50 for vaccine naïve subjects and Day 22 for vaccine non-naïve subjects). Results were then pooled across both vaccine naïve and non-naïve subjects. Homologous strains: A/H1N1=A/California/7/2009 pdm09-like virus, A/H3N2=A/Texas/50/2012, B/Yamagata=B/Massachusetts/2/2012 and B/Victoria=B/Brisbane/60/2008; B/Victoria results from Season 1 and Season 2 (aQIV) and Season 2 (comparator) are presented.	Baseline (Day 1) and 21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)
Immunogenicity Endpoint: Hemagglutination Inhibition (HI) Antibody Responses to aQIV vs TIV/QIV Against Heterologous Strains in Terms of Geometric Mean Titers (GMTs) in Subjects ≥6 to <72 Months of Age	HI GMT was assessed 21 days after last vaccination (Day 50 for vaccine naïve subjects and Day 22 for vaccine non-naive subjects) pooled GMT values across both naïve and non-naïve subjects are provided for the Day 22/50 (ie, 21 days after last vaccination); Heterologous strains: H1N1=A/Brisbane/59/2007- like; H3N2 =A/Hong Kong/4801/2014; B/Yamagata=B/Phuket/3073/2013-like; B Victoria=B/Malaysia/2506/2004; For B/Victoria results from Season 2 only are presented for both vaccine groups.	21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Heterologous Strains in Terms of Seroconversion (SC) Rates in Subjects ≥6 to <72 Months of Age	SC rates were assessed on Day 50 (ie, 21 days after two vaccinations) for vaccine naïve subjects; and on Day 22 (ie, 21 days after one vaccination) for vaccine non-naïve subjects; values pooled across naive and non-naive subjects are provided. Seroconversion is defined as HI ≥ 1:40 for subjects negative at baseline (ie, HI titer<1:10); or a minimum 4-fold increase in HI titer for subjects positive at baseline (ie, HI titer ≥ 1:10); Heterologous strains include: H1N1=A/Brisbane/59/2007- like; H3N2 =A/Hong Kong/4801/2014; B/Yamagata=B/Phuket/3073/2013- like; B Victoria=B/Malaysia/2506/2004; For B/Victoria results from Season 2 only are presented for both vaccine groups	21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)
Immunogenicity Endpoint: HI Antibody Responses to aQIV vs TIV/QIV Against Heterologous Strains in Terms of Percentage of Subjects With HI Titer ≥ 1:40 in Subjects ≥6 to <72 Months of Age	Antibody persistence was assessed as the percentage of subjects with HI titer of ≥1:40 at 21 days after last vaccination (ie, Day 50 for vaccine naïve subjects and Day 22 for vaccine non-naïve subjects). Results were then pooled across both vaccine naïve and non-naïve subjects; Heterologous strains: H1N1=A/Brisbane/59/2007- like; H3N2 =A/Hong Kong/4801/2014; B/Yamagata=B/Phuket/3073/2013- like; B Victoria=B/Malaysia/2506/2004; For B/Victoria results from Season 2 only are presented for both vaccine groups.	21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)
Safety Endpoint: Number of Subjects With Solicited Local and Systemic AEs	Subjects ≥6 to <72 months of age reporting solicited local and systemic reactions, day 1 to day 7 after vaccination with either aQIV or TIV/QIV.	7 days following each vaccination
Safety Endpoint: Number of Subjects With Unsolicited AEs, SAEs, AEs Leading to Withdrawal From the Study or Study Vaccination, NOCDs and AESIs	Safety was assessed in terms of number of subjects ≥6 to <72 months of age reporting unsolicited reactions (Day 1 to Day 50 for vaccine naïve subjects and from Day 1 to Day 22 for vaccine non-naïve subjects); Serious Adverse Events (SAEs), AEs leading to New Onset of Chronic Diseases,(NOCD), Adverse Events of Special Interests (AESI), AEs leading to withdrawal from the study or study vaccination after vaccination with either aQIV or TIV/QIV were collected up to 12 months after last vaccination.	Day 1 though Day 366 (vaccine non-naive)/Day 390 (vaccine naive)
Healthcare Utilization and Health Economic Endpoints: Number of Days of Daycare, School or Preschool Missed by Subjects Associated With RT-PCR-confirmed Influenza		within a window of 14 days after influenza-like illness (ILI)-onset
Healthcare Utilization and Health Economic Endpoint: Number of Medical Visit for Respiratory Illness Associated With RT-PCR-confirmed Influenza		within a window of 14 days after ILI-onset
Healthcare Utilization and Health Economic Endpoint: Number of Employment Days Missed by Parent(s)/Guardian(s) of Subjects With RT-PCR-confirmed Influenza		within a window of 14 days after ILI-onset
Healthcare Utilization and Health Economic Endpoint: First-occurrence of RT-PCR-confirmed Moderate-to-severe Influenza Cases as Per Prespecified Criteria in Subjects ≥6 to <72 Months of Age in Season 2.		≥21 days and ≤180 days after the last vaccination or until the end of the influenza season (Northern Hemisphere: end of June; Southern Hemisphere: end of December; Philippines/Thailand: end of October), whichever was longer

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects with a medical visit for respiratory illness associated with RT-PCR-confirmed influenza	Health Economic Outcome: To evaluate healthcare utilization and health economic outcomes	within a window of 14 days after ILI-onset
Number of employment days missed by parent(s)/guardian(s) of subjects with RT-PCR-confirmed influenza		within a window of 14 days after ILI-onset
Number of days of daycare, school or preschool missed by subjects associated with RT-PCR-confirmed influenza		within a window of 14 days after ILI-onset

Collaborators and Investigators

• Sponsor: Seqirus
• Collaborators: Novartis Vaccines

Publications and helpful links

General Publications

• Esposito S, Fling J, Chokephaibulkit K, de Bruijn M, Oberye J, Zhang B, Vossen J, Heijnen E, Smolenov I. Immunogenicity and Safety of an MF59-adjuvanted Quadrivalent Seasonal Influenza Vaccine in Young Children at High Risk of Influenza-associated Complications: A Phase III, Randomized, Observer-blind, Multicenter Clinical Trial. Pediatr Infect Dis J. 2020 Aug;39(8):e185-e191. doi: 10.1097/INF.0000000000002727.
• Vesikari T, Kirstein J, Devota Go G, Leav B, Ruzycky ME, Isakov L, de Bruijn M, Oberye J, Heijnen E. Efficacy, immunogenicity, and safety evaluation of an MF59-adjuvanted quadrivalent influenza virus vaccine compared with non-adjuvanted influenza vaccine in children: a multicentre, randomised controlled, observer-blinded, phase 3 trial. Lancet Respir Med. 2018 May;6(5):345-356. doi: 10.1016/S2213-2600(18)30108-5. Epub 2018 Apr 6.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: October 15, 2013
• First Submitted That Met QC Criteria: October 15, 2013
• First Posted (Estimate): October 17, 2013

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Influenza; children
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: V118_05; 2012-000218-12 (EudraCT Number)