Safety and Immunogenicity of Trivalent Subunit Inactivated Flu Vaccine Administered to Healthy Children and Adolescents 3 to 17 Years of Age

Seasonal Influenza Clinical Trial

Official title:

A Multi-center, Phase III, Randomized, Observer Blind Study to Evaluate the Safety, Tolerability and Immunogenicity of a Trivalent Subunit Inactivated Flu Vaccine in Healthy Children and Adolescents 3 to 17 Years of Age

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01209780
• Other study ID #: V71_18
• Status: Completed
• Phase: Phase 3
• First received: September 24, 2010
• Last updated: February 7, 2014
• Start date: September 2010
• Est. completion date: September 2011

Study information

• Verified date: February 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationPhilippines : Food and Drug AdministrationColombia: Instituto Nacional de Vigilancia de Medicamentos y AlimentosPanama: Instituto Conmemorativo Gorgas de Estudios en la SaludMexico: Comision Federal para la Protección contra Riesgos Sanitarios
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety and immunogenicity in healthy children and adolescents after one or two IM dose(s) of trivalent subunit inactivated flu vaccine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3116
• Est. completion date: September 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 3 Years to 17 Years

Eligibility

Inclusion Criteria:

• Males and females aged 3 to 17 years, in good health as determined by medical history, physical examination and clinical judgment of the investigator

• Documented consent provided by parents or legal guardians

• For individuals 8 years of age and older, informed assent to participate in the study after the nature of the study had been explained to them in terms they could understand

• Individuals and parents/guardians who were able to comply with all study procedures and were available for all clinic visits scheduled in the study

Exclusion Criteria:

• Parents or legal guardians and individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study

• Parents or legal guardians and individuals providing assent who do not consent to the retention of the subject's serum samples after study completion

• Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may have interfered with the subject's ability to participate in the study

• Individuals with history or any illness that, in the opinion of the investigator, might have interfered with the results of the study or posed additional risk to the subjects due to participation in the study

• History of any anaphylaxis, serious vaccine reactions, or hypersensitivity to influenza viral proteins, latex, to any excipients, and to eggs (including ovalbumin), chicken protein, influenza viral protein, kanamycin, neomycin sulphate, cetyltrimethylammonium bromide (CTAB), polysorbate 80, neomycin, polymixin, formaldehyde, thimerosal, beta propiolactone, or nonoxynol-9

• History of any serious disease, such as:

1. cancer

2. history of serious chronic, rheumatologic, neurologic and hematologic diseases

3. history of underlying medical condition such as inborn errors of metabolism

• Known or suspected impairment/alteration of immune function, including:

1. chronic use of oral steroids within 60 days prior to Visit 1 (use of inhaled, intranasal, or topical corticosteroids is allowed)

2. receipt of immunostimulants within 60 days prior to Visit 1

3. receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivates within 3 months prior to Visit 1 or planned during the full length of the study

4. HIV infection or HIV-related disease

• Pregnant or breast-feeding female and any positive or indeterminate pregnancy test

• Received an influenza vaccine within 6 months prior to Visit 1

• Laboratory-confirmed or suspected influenza disease within 6 months prior to Visit 1

• Receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study

• Experienced a fever and/or any acute illness within 3 days prior to each study vaccination

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Seasonal Influenza

Intervention

Biological:
• TIV
Investigational egg-derived trivalent subunit influenza vaccine.
• TIVf
US licensed trivalent inactivated subunit influenza vaccine -Fluvirin (Novartis Vaccines and Diagnostics) is approved for use in subjects =4 years.
• Comparator TIV
US licensed trivalent subunit inactivated influenza vaccine- Fluzone (Sanofi Pasteur) is approved for use in children <4 years.

Locations

Country	Name	City	State
Colombia	Centro de Atención e Investigación Medica - CAIMED	Carrera 42A # 17-50, Bogotá
Mexico	Clinical research institute ,S.C(CRI), Blvd Manuel Avila Camacho 1994 Consultorio 1103 Col. San Lucas Tepetlacalco, C.P.54055 Tlalnepantla	Estado de México
Panama	Clinica Hospital San Fernando, Floor 4 Office 419 via España las Sabanas	Panamá
Panama	Consultorios America Floor 2 Office 201-1, Via España Vista Hermosa	Panamá
Panama	Consultorios Medicos San Judas Tadeo Principal Street, Floor 5 Office 507, Villa Lucre	Panamá
Panama	Centro de Salud Magally Ruiz, Street Bolivar	Panama - La Chorrera
Philippines	Research Institute for Tropical Medicine, Department of Health Compound, FILINVEST Corporate City	Alabang, Muntinlupa City
Philippines	University of the East Ramon Magsaysay Medical Center, 64 Aurora Boulevard	Barangay Dona Imelda Quezon City
Philippines	De La Salle Health Sciences Institute	Dasmarinas Cavite
Philippines	Research Institute for Tropical Medicine, Department of Health Compound	FILINVEST Corporate City, Alabang	Muntinlupa City
Philippines	Mary Chiles General Hospital, 667 Gastambide St. Sampaloc	Manila
Philippines	Philippine Children's Medical Center, Quezon Avenue corner Agham Road	Quezon City
Philippines	Philippine General Hospital	Taft Avenue, Manila	Manila

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Countries where clinical trial is conducted

Colombia,  Mexico,  Panama,  Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion	The non-inferiority of the antibody responses of investigational TIV compared to control TIV assessed in terms of the percentage of subjects achieving seroconversion, against the three homologous vaccine strains,in children 3 to 8 years of age, at 21 days after last vaccination.; Seroconversion was defined as a pre-vaccination haemagglutinin inhibition (HI) titer <1:10 and post-vaccination HI titer =1:40 or as a pre-vaccination HI titer =1:10 and at minimum four-fold rise in post-vaccination antibody titer	Day 22 for non-naive/Day 50 for naive subjects	No
Primary	Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs)	The non-inferiority of the antibody responses of investigational TIV compared to control vaccine assessed in terms of post vaccination GMTs, at 21 days after last vaccination against the three homologous vaccine strains in 3 to 8 year old children.	Day 22 for non-naive/Day 50 for naive subjects	No
Secondary	Percentages of Subjects Achieving HI Titers =40 Following Vaccination With Investigational TIV or Control Vaccine.	The percentages of 3 to 8 year old subjects achieving HI titers =40 after receiving either one or two doses of investigational TIV or control vaccine, 21 days after last vaccination, are reported.; This criterion according to the US (CBER)guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers =40, is =70%.	Day 22 for non-naive/Day 50 for naive subjects	No
Secondary	Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine	The percentages of 3 to 8 years-old subjects achieving seroconversion in HI antibody titers after receiving either one or two doses of investigational TIV or control vaccine, at 21 days after last vaccination, are reported.; This criterion, according to the US (CBER) guideline, is met if the lower limit of 95% CI of percentage of subjects achieving seroconversion or significant increase at day 22 and day 50 (21 days after last vaccination) is =40.	Day 22 for non-naive/Day 50 for naive	No
Secondary	Percentages of Vaccine-naive Children Achieving HI Titers =40 After Receiving Two Doses of Investigational TIV or Control Vaccine.	The percentage of 3 to 8 years-old vaccine-naive subjects achieving HI titers =40, after receiving two doses of investigational TIV or control vaccine. The time frame of evaluation was 28 days after first (Day 29) and 21 days after second vaccine dose (Day 50).; This criterion according to the US (CBER) guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers =40 is =70%, for each vaccine strain.	Day 1, Day 29, and Day 50	No
Secondary	Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine	The percentages of 3 to 8 years-old vaccine naive children achieving seroconversion or significant increase in HI antibody titers after receiving two doses of investigational TIV or control vaccine, are reported. The time frame of evaluation was 28 days after first (Day 29) and 21 days after the second dose (Day 50).; This criterion, according to the US (CBER) guideline, is met if the lower limit of 95% CI of percentage of subjects achieving seroconversion or significant increase at day 29 and day 50 is =40, for each vaccine strain.	Day 29 and Day 50	No
Secondary	Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine	The number of 3-17 year old children with solicited local and systemic adverse events and other adverse events, after receiving either one or two doses of investigational TIV as compared to control vaccine are reported.	Day 1 to 7 after vaccination	Yes
Secondary	Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine	The number of 3-17 year old children reporting any unsolicited adverse event and any serious adverse event (SAE) after receiving either one or two doses of investigational TIV and control vaccine are reported.	Day 1 to 180 (non-naive )/Day 1 to 209 (naive)	Yes