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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT01346592
First received: April 30, 2011
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Influenza Disease
Biological: Trivalent split influenza vaccine (TIV)
Biological: MF59-adjuvanted trivalent influenza vaccine (aTIV)
Biological: Licensed comparator trivalent split influenza vaccine (comparator TIV)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains [ Time Frame: Day 1, Day 50 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]

    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.


  • Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains (6 to <36 Months) [ Time Frame: Day 1, Day 50 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains (6 to <24 Months) [ Time Frame: Day 1, Day 50 ] [ Designated as safety issue: No ]
    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.

  • 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) [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    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.

  • Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains (6 to <72 Months)-FAS [ Time Frame: Day 1, Day 50 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    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.

  • The HI GMTs Against Homologous Strains, by Vaccine Group [ Time Frame: Day 1, Day 29, Day 50, Day 209 ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains [ Time Frame: Day 29, Day 50, Day 209 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Subjects With HI Titers ≥40 Against Homologous Strains, by Vaccine Group [ Time Frame: Day 1, Day 29, Day 50, Day 209 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers, Against Homologous Strains [ Time Frame: Day 29, Day 50, Day 209 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 50 ] [ Designated as safety issue: No ]
    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.

  • The HI GMTs Against Heterologous Strains, by Vaccine Group (6 to <72 Months Age Group) [ Time Frame: Day 1, Day 50, Day 209 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers, Against Heterologous Strains [ Time Frame: Day 50, Day 209 ] [ Designated as safety issue: No ]
    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.

  • Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, After One Vaccination [ Time Frame: Day 1, Day 29 ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Reporting Solicited Adverse Events After Vaccination [ Time Frame: Day 1 through Day 7 after any vaccination ] [ Designated as safety issue: Yes ]
    The number of subjects reporting any solicited local and systemic adverse events (AEs), following vaccination with aTIV or licensed comparator or TIV.

  • Number of Subjects Reporting Unsolicited Adverse Events After Vaccination [ Time Frame: Day 1 to Day 394 ] [ Designated as safety issue: Yes ]
    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).


Enrollment: 6104
Study Start Date: April 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Agriflu

  Eligibility

Ages Eligible for Study:   6 Months to 72 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01346592

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

No publications provided

Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT01346592     History of Changes
Other Study ID Numbers: V70_29
Study First Received: April 30, 2011
Results First Received: January 27, 2014
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Chile: Instituto de Salud Pública de Chile
Philippines:Food and Drug Administration Philippines
South Africa:Medicine Control Council (MCC)
Australia: Therapeutic Goods Administration (TGA)

Keywords provided by Novartis:
Adjuvanted Trivalent Subunit Influenza Vaccine
vaccine
influenza
adjuvant
MF-59
pediatric

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 18, 2014