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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

Phase 3
Completed
Conditions
Influenza Disease
Interventions
Biological: MF59-adjuvanted trivalent influenza vaccine (aTIV)
Biological: Trivalent split influenza vaccine (TIV)
Biological: Licensed comparator trivalent split influenza vaccine (comparator TIV)
Registration Number
NCT01346592
Lead Sponsor
Novartis Vaccines
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
6104
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
aTIV (6 to <72 months)MF59-adjuvanted trivalent influenza vaccine (aTIV)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
TIV (6 to <72 months)Trivalent split influenza vaccine (TIV)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
Comparator TIV (6 to <72 months)Licensed comparator trivalent split influenza vaccine (comparator TIV)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
Primary Outcome Measures
NameTimeMethod
Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous StrainsDay 1, Day 50

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 StrainsDay 50

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)Day 1, Day 50

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 AgeDay 50

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
NameTimeMethod
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-FASDay 50

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-FASDay 50

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)Day 1, Day 50, Day 209

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 StrainsDay 50, Day 209

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 VaccinationDay 1, Day 29

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 VaccinationDay 1 through Day 7 after any vaccination

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 VaccinationDay 1 to Day 394

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).

Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains (6 to <24 Months)Day 1, Day 50

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)Day 50

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)-FASDay 1, Day 50

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.

Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous StrainsDay 29, Day 50, Day 209

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 GroupDay 1, Day 29, Day 50, Day 209

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 StrainsDay 29, Day 50, Day 209

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 SubgroupDay 50

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 SubgroupDay 50

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 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)-FASDay 50

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 GroupDay 1, Day 29, Day 50, Day 209

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.

Trial Locations

Locations (34)

201 Royal Children Hospital Department of Respiratory Medicine

🇦🇺

Herston, Australia

105 Mary Chiles General Hospital 667 Gastambide St Sampaloc Manila

🇵🇭

Manila, Philippines

111 DLSHI deCastro De La Salle Health Sciences Institute DBB B Dasmarinas

🇵🇭

Cavite, Philippines

104 Philippine Childrens Medical Center Quezon Avenue cor Agham Road Quezon City

🇵🇭

Quezon City, Philippines

102 University of the East Ramon Magsaysay Memorial 64 Aurora Boulevard Barangay Dona Imelda

🇵🇭

Quezon, Philippines

401 Paideia Jeronimo Salguero 2835 Piso 1

🇦🇷

Buenos Aires, Argentina

202 Sydney Children Hospital Department of Immunology and Infectious Diseases

🇦🇺

Randwick, Australia

503 Clinica Tabancura Av Tabancura 1185

🇨🇱

Santiago, Chile

205 Vaccine and Immunisation Research Group Murdoch Childrens Research Institute School Of Population Health

🇦🇺

Level 5 207 Bouverie St, Australia

502 Hospital Clinico Pontificia Universidad Catolica de Chile Marcoleta 357

🇨🇱

Santiago, Chile

403 Instituto Medico Rio Cuarto Hipolito Yrigoyen 1020

🇦🇷

Cordoba, Argentina

402 Hospital de Ninos Gallo 130

🇦🇷

Buenos Aires, Argentina

206 Vaccine and Immunology Research Trials Unit University Department of Paediatrics 2nd floor Clarence Reiger Bldg Womens and Childrens Hospital

🇦🇺

Adelaide, Australia

405 Hospital Pediatrico Nino Jesus Castro Barros 650

🇦🇷

Cordoba, Argentina

406 Hospital Nostra Senora de la Misericordia Belgrano 1500

🇦🇷

Cordoba, Argentina

204 National Centre for Immunisation Research and Surveillance Kids Research Institute The Childrens Hospital at Westmead

🇦🇺

Westmead, Australia

109 De La Salle Health Sciences Institute

🇵🇭

Dbbb Dasmarinas Cavite, Philippines

110 De La Salle Health Sciences Institute

🇵🇭

Dbbb Dasmarinas Cavite, Philippines

301 Perinatal HIV Research Unit, Baragwanath Hospital

🇿🇦

Soweto, South Africa

303 Emmed Research

🇿🇦

Pretoria, South Africa

103 Philippine General Hospital Taft Avenue

🇵🇭

Manila, Philippines

112 PGH Lim Philippine General Hospital Taft Avenue

🇵🇭

Manila, Philippines

106 Research Institute for Tropical Medicine Alabang Muntinlupa

🇵🇭

Muntinlupa, Philippines

107 Philippine General Hospital Taft Avenue

🇵🇭

Manila, Philippines

114 Philippine General Hospital Taft Avenue

🇵🇭

Manila, 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

302 Soweto Clinical Research

🇿🇦

Soweto, South Africa

108 RITM Research Institute for Tropical Medicine Department of Health Compound FILINVEST Corporate City Alabang

🇵🇭

Muntinlupa, Philippines

305 Worthwhile Clinical Trials Lakeview Hospital 1 Mowbray Avenue

🇿🇦

Benoni, South Africa

304 Newgate Centre Suite 3

🇿🇦

Johannesburg, South Africa

408 Centro de Salud 31 Serpa y Republica del Libano

🇦🇷

Mendoza, Argentina

407 Centro Pediatrico Caballito Directorio 1658

🇦🇷

Cuidad Automa de Beunos Aires, Argentina

409 Centro de Salud 16 Alpatacal y Chile

🇦🇷

Guaymallen, Argentina

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