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

Influenza Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01346592
• Other study ID #: V70_29
• Status: Completed
• Phase: Phase 3
• First received: April 30, 2011
• Last updated: March 4, 2015
• Start date: April 2011
• Est. completion date: July 2012

Study information

• Verified date: March 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaChile: Instituto de Salud Pública de ChilePhilippines:Food and Drug Administration PhilippinesSouth Africa:Medicine Control Council (MCC)Australia: Therapeutic Goods Administration (TGA)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6104
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Months to 72 Months

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Influenza Disease
• Influenza, Human

Intervention

Biological:
• Trivalent split influenza vaccine (TIV)

• MF59-adjuvanted trivalent influenza vaccine (aTIV)

• Licensed comparator trivalent split influenza vaccine (comparator TIV)

Locations

Country	Name	City	State
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	409 Centro de Salud 16 Alpatacal y Chile	Guaymallen
Argentina	408 Centro de Salud 31 Serpa y Republica del Libano	Mendoza
Australia	206 Vaccine and Immunology Research Trials Unit University Department of Paediatrics 2nd floor Clarence Reiger Bldg Womens and Childrens Hospital	Adelaide
Australia	201 Royal Children Hospital Department of Respiratory Medicine	Herston
Australia	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	204 National Centre for Immunisation Research and Surveillance Kids Research Institute The Childrens Hospital at Westmead	Westmead
Chile	502 Hospital Clinico Pontificia Universidad Catolica de Chile Marcoleta 357	Santiago
Chile	503 Clinica Tabancura Av Tabancura 1185	Santiago
Philippines	111 DLSHI deCastro De La Salle Health Sciences Institute DBB B Dasmarinas	Cavite
Philippines	109 De La Salle Health Sciences Institute	Dbbb Dasmarinas Cavite
Philippines	110 De La Salle Health Sciences Institute	Dbbb Dasmarinas Cavite
Philippines	103 Philippine General Hospital Taft Avenue	Manila
Philippines	105 Mary Chiles General Hospital 667 Gastambide St Sampaloc Manila	Manila
Philippines	107 Philippine General Hospital Taft Avenue	Manila
Philippines	112 PGH Lim Philippine General Hospital Taft Avenue	Manila
Philippines	114 Philippine General Hospital Taft Avenue	Manila
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	Muntinlupa
Philippines	102 University of the East Ramon Magsaysay Memorial 64 Aurora Boulevard Barangay Dona Imelda	Quezon
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	Quezon City
South Africa	305 Worthwhile Clinical Trials Lakeview Hospital 1 Mowbray Avenue	Benoni
South Africa	304 Newgate Centre Suite 3	Johannesburg
South Africa	303 Emmed Research	Pretoria
South Africa	301 Perinatal HIV Research Unit, Baragwanath Hospital	Soweto
South Africa	302 Soweto Clinical Research	Soweto

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Countries where clinical trial is conducted

Argentina,  Australia,  Chile,  Philippines,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes