Safety, and Immunogenicity of Two Influenza Vaccines in Healthy Subjects 3 to 64 Years Old

A Phase III, Observer-Blind, Randomized, Controlled, Multicenter Study to Evaluate Safety, Tolerability, and Immunogenicity of Two Trivalent Subunit Inactivated Influenza Vaccines in Healthy Children Aged 3 to 8 Years, in Healthy Children/Adolescents Aged 9 to 17 Years,and in Healthy Adults Aged 18 to 64 Years

This protocol is designed to evaluate safety, clinical tolerability and immunogenicity of the 2007 southern hemisphere formulation of a Novartis conventional influenza vaccine licensed in the EU and many other worldwide countries, according to the US FDA Draft Guidance for Industry "Clinical data needed to support the licensure of trivalent inactivated influenza vaccine", issued in March 2006, and to evaluate safety, clinical tolerability and immunogenicity of the 2007 southern hemisphere formulation of a Novartis conventional influenza vaccine already licensed in US. The purpose of the control arm is primarily to provide a comparative assessment for safety, not immunogenicity or effectiveness.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Influenza virus vaccine; Biological: Comparator influenza vaccine

• Study Type: Interventional
• Enrollment (Actual): 1893
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Site 2: C1425AWK
  • Cordoba, Argentina
    • Site 1: X5000BJH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 64 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy subjects 3 to 64 years of age

Exclusion Criteria:

• Receipt of other investigational products within 3 months or other vacine within 1 month;
• Allergy to eggs, egg products, or any other vaccine component;
• Laboratory confirmed influenza disease within 6 months;
• Have previously received an influenza vaccination (3 to 8 years only);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Influenza virus vaccine	Biological: Influenza virus vaccine; Two intramuscular injections of the investigational influenza virus vaccine administered 4 weeks part to group 3 to 8 years of age while one injection was administered to groups 9 to 17 years of age and 18 to 64 years of age.
Active Comparator: Comparator influenza vaccine	Biological: Comparator influenza vaccine; Two intramuscular injections were administered 4 weeks apart to group 3 to 8 years of age while one injection was administered to groups 9 to 17 years of age and 18 to 64 years of age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Seroprotection, in Healthy Adults 18 to 64 Years of Age	To evaluate immunogenicity, measured by seroprotection (percentage of subjects achieving a hemagglutination inhibition [HI] titer ≥40) after one injection of the investigational influenza virus vaccine, administered to healthy adults 18 to 64 years of age. The CBER Guidance states that the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroprotection meet or exceed 70%.	21 days after vaccination
Percentage of Subjects Achieving a Seroconversion Rate, in Adults 18 to 64 Years of Age	Seroconversion rate is defined as percentage of subjects achieving seroconversion (defined as negative pre-vaccination serum [HI<10]/ post-vaccination HI titer ≥40) or significant increase defined as at least a 4-fold increase). According to the CBER Guidance, the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconverion/significant increase meet or exceed 40%.	21 days after vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Reporting Solicited Local and Systemic Symptoms in Adults 18 to 64 Years of Age	Solicited local and systemic reactions were assessed after vaccination in adults 18 to 64 years of age.	7 days after vaccination
Percentage of Subjects With Seroprotection, in Healthy Children/Adolescents 9 to 17 Years of Age	To descriptively evaluate immunogenicity, measured by seroprotection rate (percentage of subjects achieving a hemagglutination inhibition [HI] titer ≥40) after one injection of investigational influenza virus vaccine, administered to healthy children/adolescents 9 to 17 years of age.	21 days after vaccination
Percentage of Subjects Achieving Seroconversion Rate, in Healthy Children/Adolescents 9 to 17 Years of Age	Seroconversion rate is defined as percentage of subjects achieving seroconversion (defined as negative pre-vaccination serum [HI<10]/ post-vaccination HI titer ≥40) or significant increase (defined as at least a 4-fold increase) after one injection of the investigational influenza virus vaccine, administered to healthy children/adolescents 9 to 17 years of age.	21 days after vaccination
Geometric Mean Titers (GMTs), in Healthy Children/Adolescents 9 to 17 Years of Age	To evaluate immunogenicity measured by GMTs after one injection of investigational influenza virus vaccine, administered to healthy children/adolescents 9 to 17 years of age.	21 days after vaccination
Number of Subjects Reporting Solicited Local and Systemic Symptoms in Children/Adolescents 9 to 17 Years of Age	Solicited local and systemic reactions were assessed after vaccination in children/adolescents 9 to 17 years of age.	7 days after vaccination
Percentage of Subjects With Seroprotection, in Healthy Children 3 to 8 Years of Age	To descriptively evaluate immunogenicity, measured by seroprotection rate (percentage of subjects achieving a hemagglutination inhibition [HI] titer ≥40) after two injections of the investigational influenza virus vaccine, in healthy children 3 to 8 years of age.	50 days after last vaccination
Percentage of Subjects Achieving Seroconversion Rate, in Healthy Children 3 to 8 Years of Age	Seroconversion rate is defined as percentage of subjects achieving seroconversion (defined as negative pre-vaccination serum [HI<10]/ post-vaccination HI titer ≥40) or significant increase (defined as at least a 4-fold increase) after two injections of the investigational influenza virus vaccine, in healthy children 3 to 8 years of age.	50 days after last vaccination
Geometric Mean Titers (GMTs), in Healthy Children 3 to 8 Years of Age	To evaluate immunogenicity measured by GMTs after two injections of the investigational influenza virus vaccine, in healthy children 3 to 8 years of age.	50 days after last vaccination
Number or Subjects Reporting Solicited Local and Systemic Symptoms, in Healthy Children 3 to 8 Years of Age.	Solicited local and systemic reactions were assessed after each vaccination, in healthy children 3 to 8 years of age.	7 days after each vaccination
Geometric Mean Titers (GMTs), in Healthy Adults 18 to 64 Years of Age	Immunogenicity measured by GMTs after one injection of the investigational influenza virus vaccine, in healthy adults 18 to 64 years of age.	21 days after vaccination

Collaborators and Investigators

• Sponsor: Novartis
• Collaborators: Novartis Vaccines

Publications and helpful links

General Publications

• Tregnaghi MW, Stamboulian D, Vanadia PC, Tregnaghi JP, Calvari M, Fragapane E, Casula D, Pellegrini M, Groth N. Immunogenicity, safety, and tolerability of two trivalent subunit inactivated influenza vaccines: a phase III, observer-blind, randomized, controlled multicenter study. Viral Immunol. 2012 Jun;25(3):216-25. doi: 10.1089/vim.2011.0063.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: April 23, 2007
• First Submitted That Met QC Criteria: April 23, 2007
• First Posted (Estimate): April 24, 2007

Study Record Updates

• Last Update Posted (Estimate): October 1, 2015
• Last Update Submitted That Met QC Criteria: September 16, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Influenza, Egg-Derived, Healthy Children, Healthy Adolescents, Healthy Adults, Safety, Immunogenicity, Trivalent, Inactivated, Vaccination
• 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: V71P5; IND: 13299