Safety, Tolerability, and Immunogenicity of the Adjuvanted Trivalent Subunit Influenza Vaccine and the Non-Adjuvanted Trivalent Subunit Influenza Vaccine Compared to the Non-Adjuvanted Trivalent Split Influenza Vaccine in Children 6 to < 72 Months of Age

A Phase III, Observer-Blind, Randomized, Multi-center Study to Evaluate the Safety, Tolerability, and Immunogenicity of Fluad and Agriflu Compared to the Non-adjuvanted Trivalent Influenza Vaccine Fluzone in Children 6 to < 72 Months of Age

This Study Aims to Evaluate the Safety, Tolerability, and Immunogenicity of the Adjuvanted Trivalent Subunit Influenza Vaccine and the Non-Adjuvanted Trivalent Subunit Influenza Vaccine Compared to the Non-Adjuvanted Trivalent Split Influenza Vaccine in Children 6 to < 72 Months of Age.

Study Overview

• Status: Completed
• Conditions: Influenza Disease
• Intervention / Treatment: Biological: MF59-adjuvanted trivalent influenza vaccine (aTIV); Biological: Licensed comparator trivalent split influenza vaccine (comparator TIV); Biological: Trivalent split influenza vaccine (TIV)

• Study Type: Interventional
• Enrollment (Actual): 6104
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • 401 Paideia Jeronimo Salguero 2835 Piso 1
  • Buenos Aires, Argentina
    • 402 Hospital de Ninos Gallo 130
  • Cordoba, Argentina
    • 403 Instituto Medico Rio Cuarto Hipolito Yrigoyen 1020
  • Cordoba, Argentina
    • 405 Hospital Pediatrico Nino Jesus Castro Barros 650
  • Cordoba, Argentina
    • 406 Hospital Nostra Senora de la Misericordia Belgrano 1500
  • Cuidad Automa de Beunos Aires, Argentina, 1406
    • 407 Centro Pediatrico Caballito Directorio 1658
  • Guaymallen, Argentina
    • 409 Centro de Salud 16 Alpatacal y Chile
  • Mendoza, Argentina
    • 408 Centro de Salud 31 Serpa y Republica del Libano
• Australia
  • Adelaide, Australia, 5006
    • 206 Vaccine and Immunology Research Trials Unit University Department of Paediatrics 2nd floor Clarence Reiger Bldg Womens and Childrens Hospital
  • Herston, Australia, 4029
    • 201 Royal Children Hospital Department of Respiratory Medicine
  • Level 5 207 Bouverie St, Australia
    • 205 Vaccine and Immunisation Research Group Murdoch Childrens Research Institute School Of Population Health
  • Randwick, Australia, 2031
    • 202 Sydney Children Hospital Department of Immunology and Infectious Diseases
  • Westmead, Australia, 2145
    • 204 National Centre for Immunisation Research and Surveillance Kids Research Institute The Childrens Hospital at Westmead
• Chile
  • Santiago, Chile
    • 502 Hospital Clinico Pontificia Universidad Catolica de Chile Marcoleta 357
  • Santiago, Chile
    • 503 Clinica Tabancura Av Tabancura 1185
• Philippines
  • Cavite, Philippines, 4114
    • 111 DLSHI deCastro De La Salle Health Sciences Institute DBB B Dasmarinas
  • Dbbb Dasmarinas Cavite, Philippines, 4114
    • 109 De La Salle Health Sciences Institute
  • Dbbb Dasmarinas Cavite, Philippines, 4114
    • 110 De La Salle Health Sciences Institute
  • Manila, Philippines, 1000
    • 103 Philippine General Hospital Taft Avenue
  • Manila, Philippines, 1000
    • 107 Philippine General Hospital Taft Avenue
  • Manila, Philippines, 1000
    • 112 PGH Lim Philippine General Hospital Taft Avenue
  • Manila, Philippines, 1000
    • 114 Philippine General Hospital Taft Avenue
  • Manila, Philippines, 1008
    • 105 Mary Chiles General Hospital 667 Gastambide St Sampaloc Manila
  • Muntinlupa, Philippines
    • 106 Research Institute for Tropical Medicine Alabang Muntinlupa
  • Muntinlupa, Philippines
    • 108 RITM Research Institute for Tropical Medicine Department of Health Compound FILINVEST Corporate City Alabang
  • Quezon, Philippines
    • 102 University of the East Ramon Magsaysay Memorial 64 Aurora Boulevard Barangay Dona Imelda
  • Quezon City, Philippines
    • 101 Philippine Childrens Medical Center Quezon Avenue cor Agham Road Quezon City
  • Quezon City, Philippines
    • 104 Philippine Childrens Medical Center Quezon Avenue cor Agham Road Quezon City
  • Quezon City, Philippines
    • 113 Philippine Childrens Medical Center Quezon Avenue cor Agham Road Quezon City
• South Africa
  • Benoni, South Africa, 1500
    • 305 Worthwhile Clinical Trials Lakeview Hospital 1 Mowbray Avenue
  • Johannesburg, South Africa, 2113
    • 304 Newgate Centre Suite 3
  • Pretoria, South Africa, 0084
    • 303 Emmed Research
  • Soweto, South Africa
    • 301 Perinatal HIV Research Unit, Baragwanath Hospital
  • Soweto, South Africa
    • 302 Soweto Clinical Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1.Children 6 months to 72 months of age.

Exclusion Criteria:Children

1. Who had been hospitalized at the time of enrollment
2. Who had any serious reaction or hypersensitivity to any vaccine component, eggs, or chicken protein
3. Who had known impairment of the immune function
4. Who had fever interfering with normal daily activities at the time of enrollment
5. Who had received licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in the study
6. Concomitant participation in another clinical study
7. Who had surgery planned during the study period that in the investigator's opinion would have interfered with the study visits schedule.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: aTIV (6 to <72 months); Subjects received an investigational MF59-adjuvanted trivalent influenza vaccine (aTIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29	Biological: MF59-adjuvanted trivalent influenza vaccine (aTIV); Other Names: Fluad
ACTIVE_COMPARATOR: Comparator TIV (6 to <72 months); Subjects received a licensed comparator trivalent split influenza vaccine (comparator TIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29	Biological: Licensed comparator trivalent split influenza vaccine (comparator TIV); Other Names: Fluzone
ACTIVE_COMPARATOR: TIV (6 to <72 months); Subjects received an investigational trivalent split influenza vaccine (TIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29	Biological: Trivalent split influenza vaccine (TIV); Other Names: Agriflu

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains	The non-inferiority of Hemagglutination Inhibition (HI) antibody responses of aTIV compared to TIV and comparator TIV assessed in terms of post vaccination GMTs at three weeks after last vaccination against the three homologous vaccine strains.	Day 1, Day 50
Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titers Against Homologous Strains	The non-inferiority of HI antibody responses of aTIV compared to TIV and comparator TIV assessed in terms of percentage of subjects achieving seroconversion or ≥4-fold increase in HI titers at three weeks after last vaccination against the three homologous vaccine strains. Seroconversion defined as prevaccination HI titer <10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.	Day 50
Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains (6 to <36 Months)	The non-inferiority of HI antibody responses of TIV to that of comparator TIV, in subjects aged 6 to <36 Months, assessed in terms of post vaccination GMTs at three weeks after last vaccination against the three homologous vaccine strains.	Day 1, Day 50
Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains in Subjects 6 to <36 Months of Age	The non-inferiority of HI antibody responses of TIV to that of the licensed comparator TIV assessed in terms of percentage of subjects achieving seroconversion or ≥4-fold increase in HI titers at three weeks after last vaccination against the three homologous vaccine strains.	Day 50

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains (6 to <24 Months)	The superiority of HI antibody responses, in subjects 6 to <24 months of age, of aTIV compared to TIV and comparator TIV assessed in terms of post vaccination GMTs at three weeks after last vaccination against the three homologous vaccine strains.	Day 1, Day 50
Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains (6 to <24 Months)	The superiority of HI antibody responses, in subjects 6 to <24 months of age, of aTIV compared to TIV and comparator TIV assessed in terms of number of subjects achieving seroconversion at three weeks after last vaccination against the three homologous vaccine strains.	Day 50
Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains (6 to <72 Months)-FAS	The superiority of HI antibody responses, in subjects 6 to <72 months of age, of aTIV compared to TIV and comparator TIV assessed in terms of post vaccination GMTs at three weeks after last vaccination against the three homologous vaccine strains.	Day 1, Day 50
Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers Against Homologous Strains (6 to <72 Months)-FAS	The superiority of HI antibody responses, in subjects 6 to <24 months of age, of aTIV compared to TIV and comparator TIV assessed in terms of number of subjects achieving seroconversion ≥4 fold increase in HI titers at three weeks after last vaccination against the three homologous vaccine strains.	Day 50
The HI GMTs Against Homologous Strains, by Vaccine Group	The HI antibody titers against the three homologous strains following vaccination with either aTIV, licensed comparator or TIV, at three weeks and at six months after vaccination are reported as GMTs.	Day 1, Day 29, Day 50, Day 209
Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains	The GMR of post-vaccination versus pre-vaccination HI titers against homologous strains, three weeks (day 29/day 1; day 50/day 1)and six months (day 209/day 1) after vaccination with either aTIV, licensed comparator or TIV.	Day 29, Day 50, Day 209
Percentage of Subjects With HI Titers ≥40 Against Homologous Strains, by Vaccine Group	The percentage of subjects demonstrating HI titers ≥40,against homologous strains, at three weeks and six months after vaccination with aTIV or licensed comparator or TIV.	Day 1, Day 29, Day 50, Day 209
Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers, Against Homologous Strains	The percentage of subjects achieving seroconversion ≥4 fold increase in HI titers from baseline, against homologous strains, at three weeks and six months after vaccination with ATIV or licensed comparator or TIV.	Day 29, Day 50, Day 209
Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, Subjects at Risk/Not at Risk, by Age Subgroup	The non-inferiority of Hemagglutination Inhibition (HI) antibody responses of aTIV compared to TIV and comparator TIV assessed in terms of post vaccination GMTs at three weeks after last vaccination against the three homologous vaccine strains, in subjects with a defined set of underlying medical conditions (at risk) and healthy subjects (not at risk), by age sub group.	Day 50
Comparison of Antibody Responses of aTIV Versus Comparator TIV and TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains in Subjects at Risk/Not at Risk, by Age Subgroup	The non-inferiority of HI antibody responses of aTIV to that of the licensed comparator TIV and to investigational TIV was assessed in terms of percentage of subjects achieving seroconversion or ≥4-fold increase in HI titers at three weeks after last vaccination against the three homologous vaccine strains in subjects with a defined set of underlying medical conditions (at risk) and in healthy subjects (not at risk) , by age sub group.	Day 50
Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains in Subjects at Risk/Not at Risk, by Age Sub Group-FAS	The superiority of HI antibody responses of aTIV compared to TIV and comparator TIV assessed in terms of of percentage of subjects achieving seroconversion or ≥4-fold increase in HI Titer at three weeks after last vaccination against the three homologous vaccine strains in subjects with a defined set of underlying medical conditions (at risk) and healthy subjects (not at risk), by age sub group.	Day 50
Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, at Risk/Not at Risk, by Age Sub Group-FAS	The superiority of HI antibody responses of aTIV compared to TIV and comparator TIV assessed in terms of post vaccination GMTs at three weeks after last vaccination against the three homologous vaccine strains, in subjects with a defined set of underlying medical conditions (at risk) and in healthy subjects (not at risk), by age sub group.	Day 50
The HI GMTs Against Heterologous Strains, by Vaccine Group (6 to <72 Months Age Group)	The HI antibody titers against the heterologous strains following vaccination with either aTIV, licensed comparator or TIV, at three weeks and at six months after vaccination are reported as GMTs.	Day 1, Day 50, Day 209
Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers, Against Heterologous Strains	The percentage of subjects achieving seroconversion or ≥4 fold increase in HI titers from baseline, against heterologous strains, at three weeks and six months after last vaccination with aTIV or licensed comparator or TIV.	Day 50, Day 209
Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, After One Vaccination	To demonstrate the GMTs at three weeks after one dose of aTIV are statistically significantly higher to the corresponding response's of comparator TIV and TIV.	Day 1, Day 29
Number of Subjects Reporting Solicited Adverse Events After Vaccination	The number of subjects reporting any solicited local and systemic adverse events (AEs), following vaccination with aTIV or licensed comparator or TIV.	Day 1 through Day 7 after any vaccination
Number of Subjects Reporting Unsolicited Adverse Events After Vaccination	The number of subjects reporting any unsolicited adverse events (AEs) between Day 1 to Day 50, serious adverse events (SAEs), AE leading to withdrawal (WD), new onset of chronic disease(NOCD), adverse events of special interest following vaccination with aTIV or licensed comparator or TIV throughout the study (Day 1 to Day 394).	Day 1 to Day 394

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Publications and helpful links

General Publications

• Nolan T, Bravo L, Ceballos A, Mitha E, Gray G, Quiambao B, Patel SS, Bizjajeva S, Bock H, Nazaire-Bermal N, Forleo-Neto E, Cioppa GD, Narasimhan V. Enhanced and persistent antibody response against homologous and heterologous strains elicited by a MF59-adjuvanted influenza vaccine in infants and young children. Vaccine. 2014 Oct 21;32(46):6146-56. doi: 10.1016/j.vaccine.2014.08.068. Epub 2014 Sep 16.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (ACTUAL): July 1, 2012
• Study Completion (ACTUAL): July 1, 2012

Study Registration Dates

• First Submitted: April 30, 2011
• First Submitted That Met QC Criteria: May 2, 2011
• First Posted (ESTIMATE): May 3, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): March 26, 2015
• Last Update Submitted That Met QC Criteria: March 4, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: pediatric; vaccine; influenza; adjuvant; Adjuvanted Trivalent Subunit Influenza Vaccine; MF-59
• 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: V70_29