Clinical trial NCT01964989: Clinical Study to Evaluate the Safety, Immunogenicity and Efficacy of Investigational Flu Vaccine Compared to Approved Flu Vaccine in Children.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza Virus
Keywords: Influenza
children
Lead sponsor: Seqirus
Sponsor class: INDUSTRY
Collaborators: name: Novartis Vaccines
First posted: 2013-10-17
Enrollment: 10644
Sex: ALL
Minimum age (years): 6
Maximum age (years): 71
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: ≥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 outcomes:
measure: 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.
timeFrame: ≥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
measure: 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
timeFrame: ≥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
measure: 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
timeFrame: ≥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
measure: 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
timeFrame: ≥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
measure: 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
timeFrame: ≥7 days and at ≥14 days after first vaccination up to day of second vaccination
measure: 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.
timeFrame: ≥7 days and ≤21 days after the last vaccination
measure: 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
timeFrame: 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
measure: 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
timeFrame: Day 29 and Day 50
measure: 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
timeFrame: Baseline (Day 1) and 21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)
measure: 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
timeFrame: 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
measure: 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
timeFrame: Baseline (Day 1) and 21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)
measure: 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
timeFrame: Baseline (Day 1) and 180 days after the last vaccination (Day 209 for vaccine naive subjects; Day 181 for vaccine non-naïve subjects)
measure: 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
timeFrame: Baseline (Day 1) and 21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)
measure: 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
timeFrame: 21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)
measure: 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
timeFrame: 21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)
measure: 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
timeFrame: 21 days after the last vaccination (Day 50 for vaccine naive subjects; Day 22 for vaccine non-naïve subjects)
measure: Safety Endpoint: Number of Subjects With Solicited Local and Systemic AEs
timeFrame: 7 days following each vaccination
measure: Safety Endpoint: Number of Subjects With Unsolicited AEs, SAEs, AEs Leading to Withdrawal From the Study or Study Vaccination, NOCDs and AESIs
timeFrame: Day 1 though Day 366 (vaccine non-naive)/Day 390 (vaccine naive)
measure: Healthcare Utilization and Health Economic Endpoints: Number of Days of Daycare, School or Preschool Missed by Subjects Associated With RT-PCR-confirmed Influenza
timeFrame: within a window of 14 days after influenza-like illness (ILI)-onset
measure: Healthcare Utilization and Health Economic Endpoint: Number of Medical Visit for Respiratory Illness Associated With RT-PCR-confirmed Influenza
timeFrame: within a window of 14 days after ILI-onset
measure: Healthcare Utilization and Health Economic Endpoint: Number of Employment Days Missed by Parent(s)/Guardian(s) of Subjects With RT-PCR-confirmed Influenza
timeFrame: within a window of 14 days after ILI-onset
measure: 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.
timeFrame: ≥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 outcomes:
Locations:
city: Chandler
country: United States
facility: 222, Novartis Investigational Site
state: Arizona
city: Harrisburg
country: United States
facility: 267, Novartis Investigational Site
state: Arkansas
city: Anaheim
country: United States
facility: 259, Novartis Investigational Site
state: California
city: Anaheim
country: United States
facility: 280, Novartis Investigational Site
state: California
city: Baldwin Park
country: United States
facility: 213, Novartis Investigational Site
state: California
city: Downey
country: United States
facility: 407, Novartis Investigational Site
state: California
city: La Puente
country: United States
facility: 238, Novartis Investigational Site
state: California
city: Ontario
country: United States
facility: 411, Novartis Investigational Site
state: California
city: Paramount
country: United States
facility: 202, Novartis Investigational Site
state: California
city: San Diego
country: United States
facility: 250, Novartis Investigational Site
state: California
city: San Francisco
country: United States
facility: 293, Novartis Investigational Site
state: California
city: Colorado Springs
country: United States
facility: 243, Novartis Investigational Site
state: Colorado
city: Denver
country: United States
facility: 249, Novartis Investigational Site
state: Colorado
city: Boca Raton
country: United States
facility: 229, Novartis Investigational Site
state: Florida
city: Hialeah
country: United States
facility: 416, Novartis Investigational Site
state: Florida
city: Hialeah
country: United States
facility: 287, Novartis Investigational Site
state: Florida
city: Homestead
country: United States
facility: 412, Novartis Investigational Site
state: Florida
city: Melbourne
country: United States
facility: 224, Novartis Investigational Site
state: Florida
city: Miami
country: United States
facility: 417, Novartis Investigational Site
state: Florida
city: Miami
country: United States
facility: 404, Novartis Investigational Site
state: Florida
city: Miami
country: United States
facility: 285, Novartis Investigational Site
state: Florida
city: Miami
country: United States
facility: 277,Novartis Investigational Site
state: Florida
city: Opa-locka
country: United States
facility: 234, Novartis Investigational Site
state: Florida
city: Orlando
country: United States
facility: 297, Novartis Investigational Site
state: Florida
city: Orlando
country: United States
facility: 297, Novartis Investigational vaccine
state: Florida
city: Sarasota
country: United States
facility: 410, Novartis Investigational Site
state: Florida
city: Atlanta
country: United States
facility: 401, Novartis iNvestiagtional Site
state: Georgia
city: DeKalb
country: United States
facility: 299, Novartis Investigational Site
state: Illinois
city: Peoria
country: United States
facility: 268, Novartis Investigational Site
state: Illinois
city: Augusta
country: United States
facility: 209, Novartis Investigational Site
state: Kansas
city: Newton
country: United States
facility: 210, Novartis Investigational Site
state: Kansas
city: Park City
country: United States
facility: 274 Novartis Investigational Site
state: Kansas
city: Wichita
country: United States
facility: 211, Novartis Investigational Site
state: Kansas
city: Bardstown
country: United States
facility: 269, Novartis Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: 226, Novartis Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: 248, Novartis Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: 207, Novartis Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: 290, Novartis Investigational Site
state: Kentucky
city: Haughton
country: United States
facility: 265, Novartis Investigational Site
state: Louisiana
city: Mangham
country: United States
facility: 408, Novartis Investigational Site
state: Louisiana
city: Metairie
country: United States
facility: 225, Novartis Investigational Site
state: Louisiana
city: Metairie
country: United States
facility: 233, Novartis Investigational Site
state: Louisiana
city: Monroe
country: United States
facility: 418, Novartis Investigational SIte
state: Louisiana
city: Annapolis
country: United States
facility: 262, Novartis Investigational site
state: Maryland
city: Frederick
country: United States
facility: 263, Novartis Investigational Site
state: Maryland
city: Silver Spring
country: United States
facility: 405, Novartis Investigational Site
state: Maryland
city: Saint Paul
country: United States
facility: 278, Novartis Investigational Site
state: Minnesota
city: Bellevue
country: United States
facility: 221, Novartis Investigational Site
state: Nebraska
city: Fremont
country: United States
facility: 219, Novartis Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: 402, Novartis Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: 288, Novartis Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: 228, Novartis Investigational Site
state: Nebraska
city: Henderson
country: United States
facility: 244, Novartis Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: 286, Novartis Investigational site
state: Nevada
city: Binghamton
country: United States
facility: 255, Novartis Investigational Site
state: New York
city: Brooklyn
country: United States
facility: 414, Novartis Investigational Site
state: New York
city: Syracuse
country: United States
facility: 264, Novartis Investigational Site
state: New York
city: Boone
country: United States
facility: 409, Novartis Investigational Site
state: North Carolina
city: Cary
country: United States
facility: 266, Novartis Investigational Site
state: North Carolina
city: Clyde
country: United States
facility: 403, Novartis Investigational Site
state: North Carolina
city: Akron
country: United States
facility: 240, Novartis Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: 254, Novartis Investigational Site
state: Ohio
city: Dayton
country: United States
facility: 245, Novartis Investigational Site
state: Ohio
city: Dayton
country: United States
facility: 281, Novartis Investigational Site
state: Ohio
city: Dayton
country: United States
facility: 281, Novartis Investigational vaccines
state: Ohio
city: Tulsa
country: United States
facility: 256, Novartis Investigational Site
state: Oklahoma
city: Erie
country: United States
facility: 292, Novartis Investigational Site
state: Pennsylvania
city: Scottdale
country: United States
facility: 270, Novartis Investigational Site
state: Pennsylvania
city: Anderson
country: United States
facility: 220, Novartis Investigational Site
state: South Carolina
city: Barnwell
country: United States
facility: 406, novartis Investigational Site
state: South Carolina
city: Charleston
country: United States
facility: 272, Novartis Investigational Site
state: South Carolina
city: Moncks Corner
country: United States
facility: 232, Novartis Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: 291, Novartis Investigational vaccine
state: South Carolina
city: Nashville
country: United States
facility: 283, Novartis Investigational Site
state: Tennessee
city: Austin
country: United States
facility: 208, Novartis Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: 247, Novartis Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: 217, Novartis Investigational Site
state: Texas
city: San Angelo
country: United States
facility: 214, Novartis Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 400, Novartis investigational Site
state: Texas
city: Tomball
country: United States
facility: 260, Novartis Investigational Site
state: Texas
city: Layton
country: United States
facility: 295, Novartis Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: 236, Novartis Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: 212, Novartis Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: 246, Novartis Investigational Site
state: Utah
city: Spanish Fork
country: United States
facility: 279, Novartis Investigational Site
state: Utah
city: Syracuse
country: United States
facility: 282, Novartis Investigational Site
state: Utah
city: West Haven
country: United States
facility: 294, Novartis Investigational Site
state: Utah
city: West Jordan
country: United States
facility: 201, Novartis Investigational Site
state: Utah
city: West Jordan
country: United States
facility: 271, Novartis Investigational Site
state: Utah
city: Burke
country: United States
facility: 251, Novartis Investigational Site
state: Virginia
city: Vienna
country: United States
facility: 296, Novartis Investigational Site
state: Virginia
city: Newmarket
country: Canada
facility: 180, Novartis Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: 184, Novartis Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 182,Novartis Investigational Site
state: Ontario
city: Quebec
country: Canada
facility: 186, Novartis Investigational Site
city: Québec
country: Canada
facility: 183, Novartis Investigational Site
city: Espoo
country: Finland
facility: 001, Novartis Investigational Site
city: Helsinki
country: Finland
facility: 003, Novartis Investigational Site
city: Helsinki
country: Finland
facility: 002, Novartis Investigational Site
city: Järvenpää
country: Finland
facility: 004, Novartis Investigational Site
city: Kokkola
country: Finland
facility: 005, Novartis Investigational Site
city: Oulu
country: Finland
facility: 006, Novartis Investigational Site
city: Pori
country: Finland
facility: 007, Novartis Investigational Site
city: Seinäjoki
country: Finland
facility: 008, Novartis Investigational Site
city: Tampere
country: Finland
facility: 009, Novartis Investigational Site
city: Turku
country: Finland
facility: 010, Novartis Investigational Site
city: Vantaa
country: Finland
facility: 011, Novartis Investigational Site
city: Florence
country: Italy
facility: 030, Novartis Investigational Site
city: Genova
country: Italy
facility: 023, Novartis Investigational Site
city: Milano
country: Italy
facility: 020, Novartis Investigational Site
city: Milano
country: Italy
facility: 026, Novartis Investigational Site
city: Napoli
country: Italy
facility: 025, Novartis Investigational Site
city: Novara
country: Italy
facility: 021, Novartis Investigational Site
city: Padova
country: Italy
facility: 022, Novartis Investigational Site
city: Pisa
country: Italy
facility: 024, Novartis Investigational Site
city: Sassari
country: Italy
facility: 028, Novartis Investigational Site
city: Morelia
country: Mexico
facility: 173, Novartis Investigational Site
state: Michoacan
city: Durango
country: Mexico
facility: 176, Novartis Investigational Site
city: Mexico
country: Mexico
facility: 170, Novartis Investigational Site
city: Mexico
country: Mexico
facility: 177, Novartis Investigational Site
city: Mexico
country: Mexico
facility: 178, Novartis Investigational Site
city: Mexico
country: Mexico
facility: 175, Novartis Investigational Site
city: Dasmariñas
country: Philippines
facility: 300, Novartis Investigational Site
state: Cavite
city: Alabang
country: Philippines
facility: 306, Novartis Investigational Site
state: Muntilupa
city: Manila
country: Philippines
facility: 302, Novartis Investigational Site
city: Manila
country: Philippines
facility: 301, Novartis Investigational Site
city: Muntinlupa
country: Philippines
facility: 303, Novartis Investigational Site
city: Muntinlupa
country: Philippines
facility: 304, Novartis Investigational Site
city: Muntinlupa
country: Philippines
facility: 305, Novartis Investigational Site
city: Debica
country: Poland
facility: 040, Novartis Investigational Site
city: Katowice
country: Poland
facility: 042, Novartis Investigational Site
city: Leczna
country: Poland
facility: 052, Novartis Investigational Site
city: Lodz
country: Poland
facility: 048, Novartis Investigational Site
city: Lubartow
country: Poland
facility: 049, Novartis Investigational Site
city: Oborniki Slaskie
country: Poland
facility: 051, Novartis Investigational Site
city: Osielsko
country: Poland
facility: 046, Novartis Investigational Site
city: Siemianowice Slaskie
country: Poland
facility: 043, Novartis Investigational Site
city: Tarnow
country: Poland
facility: 047, Novartis Investigational Site
city: Warszawa
country: Poland
facility: 041, Novartis Investigational Site
city: Warszawa
country: Poland
facility: 050, Novartis Investigational Site
city: Wola
country: Poland
facility: 045, Novartis Investigational Site
city: Wroclaw
country: Poland
facility: 044, Novartis Investigational Site
city: Ponce
country: Puerto Rico
facility: 257, Novartis Investigational Site
city: San Juan
country: Puerto Rico
facility: 415, Novartis Investigational vaccine
city: San Juan
country: Puerto Rico
facility: 415, Novartis Investigational Site
city: Sabadell
country: Spain
facility: 80, Novartis Investigational Site
state: Barcelona
city: Santiago
country: Spain
facility: 075, Novartis Investigational Site
state: Galicia
city: Granada
country: Spain
facility: 074, Novartis Investigational Site
city: Madrid
country: Spain
facility: 076, Novartis Investigational Site
city: Madrid
country: Spain
facility: 077, Novartis Investigational Site
city: Malaga
country: Spain
facility: 79, Novartis Investigational Site
city: Valencia
country: Spain
facility: 078, Novartis Investigational Site
city: Banciao
country: Taiwan
facility: 343, Novartis Investigational Site
state: New Taipei City
city: Datong
country: Taiwan
facility: 346, Novartis Investigational Site
state: Taipei City
city: Taichung
country: Taiwan
facility: 344, Novartis Investigational Site
city: Taichung
country: Taiwan
facility: 345, Novartis Investigational Site
city: Taipei City
country: Taiwan
facility: 340, Novartis Investigational Site
city: Taipei City
country: Taiwan
facility: 341, Novartis Investigational Site
city: Taoyuan
country: Taiwan
facility: 342, Novartis Investigational Site
city: Bangkoknoi
country: Thailand
facility: 321, Novartis Investigational Site
state: Bangkok
city: Bangkoknoi
country: Thailand
facility: 322, Novartis Investigational Site
state: Bangkok
city: Pathum Wan
country: Thailand
facility: 323, Novartis Investigational Site
state: Bangkok
city: Ratchathewi
country: Thailand
facility: 327, Novartis Investigational Site
state: Bangkok
city: Pathum Thani
country: Thailand
facility: 325, Novartis Investigational Site
state: Prathumthani
city: Hat Yai
country: Thailand
facility: 326, Novartis Investigational Site
state: Songkhia
city: Bangkok
country: Thailand
facility: 320, Novartis Investigational Site
city: Bangkok
country: Thailand
facility: 324, Novartis Investigational Site
Study officials:
affiliation: Seqirus
name: Clinical Program Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.