Study to Evaluate the Consistency of Three Consecutive Production Lots of Influenza Vaccine in Healthy Subjects 18 to 49 Years Old

A Phase III, Randomized, Controlled, Observer-Blind, Single-Center Study to Evaluate the Consistency of Three Consecutive Lots of a Trivalent Subunit Influenza Vaccine Produced in Embryonated Hen Eggs in Healthy Subjects Aged 18 to 49 Years

The purpose of this research is to demonstrate immunologic equivalence of three consecutive production lots of the subunit influenza vaccine compared to egg-derived inactivated influenza vaccine in healthy subjects 18 to 49 years of ages. In addition, this study is to show how safe and well tolerated a conventional inactivated subunit influenza vaccine, licensed in many countries outside the United States, is compared to an inactivated influenza vaccine, licensed in the United States.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Lot A of Influenza virus vaccine; Biological: Lot B of Influenza virus vaccine; Biological: Lot C of Influenza virus vaccine; Biological: All 3 consecutive lots of influenza virus vaccine pooled; Biological: Comparator influenza virus vaccine

• Study Type: Interventional
• Enrollment (Actual): 1507
• Phase: Phase 3

Contacts and Locations

Study Locations

• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Centro de Salud Galvan
  • Santo Domingo, Dominican Republic
    • Hosp. Nuestra Sra. Altagracia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 to 49 years of age;
• In good health as determined by medical history and physical examination;
• Able and willing to provide written informed consent prior to any study procedure;
• Able to comply with all study procedures and available for all clinic visits scheduled in the study.

Exclusion Criteria:

• Any serious disease, such as: cancer, autoimmune disease (including rheumatoid arthritis), advanced arteriosclerotic disease or complicated diabetes mellitus
• History of any anaphylaxis, serious vaccine reactions, or hypersensitivity to eggs, egg protein, chicken feathers, influenza viral protein, neomycin, polymyxin, or any other vaccine component, chemically related substance, or component of the potential packaging materials (latex);
• Known or suspected impairment/alteration of immune function
• Receipt of an influenza vaccine within 6 months prior to Visit 1;
• Current drug or alcohol abuse or a history of drug or alcohol abuse that in the investigator's opinion would interfere with safety of the subject or the evaluation of the study objectives;
• Laboratory-confirmed influenza disease within 6 months prior to Visit 1

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Influenza virus vaccine (lot A); Lot A of the investigational influenza virus vaccine	Biological: Lot A of Influenza virus vaccine; 1 injection of the trivalent subunit influenza virus vaccine (lot A) administered intramuscularly
Experimental: Influenza virus vaccine (lot B); Lot B of the investigational influenza virus vaccine	Biological: Lot B of Influenza virus vaccine; 1 injection of the trivalent subunit influenza virus vaccine (lot B) administered intramuscularly
Experimental: Influenza virus vaccine (lot C); Lot C of the investigational influenza virus vaccine	Biological: Lot C of Influenza virus vaccine; 1 injection of the trivalent subunit influenza virus vaccine (lot C) administered intramuscularly
Experimental: Influenza virus vaccine (pooled); Pooled data of all three lots (Lot A, B and C) of the investigational influenza virus vaccine	Biological: All 3 consecutive lots of influenza virus vaccine pooled; 1 injection of the pooled trivalent subunit influenza virus vaccine administered intramuscularly
Active Comparator: Comparator influenza vaccine; A US licensed influenza virus vaccine	Biological: Comparator influenza virus vaccine; 1 injection of the trivalent subunit influenza virus vaccine administered intramuscularly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs), by Vaccine Lots	The immunologic equivalence of three consecutive production lots of the influenza virus vaccine was measured in terms of GMTs for all vaccine influenza strains.	21 days after vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs), by Vaccine Group and Strain	The GMTs and 95% CIs were calculated for each of the vaccine group (three consecutive production lots pooled for the investigational influenza virus vaccine and comparator) and for each strain.	21 days after vaccination
Number of Subjects Reporting Solicited Local and Systemic Symptoms	Solicited local and systemic reactions were assessed after vaccination for the two vaccines (three consecutive production lots pooled for the investigational influenza virus vaccine and comparator) and for each of the three consecutive production lots of the investigational influenza virus vaccine.	7 days after vaccination
Number of Subjects With at Least One Unsolicited Adverse Event	Number of subjects reporting at least one unsolicited adverse event, regardless of the assessement of relatedness to the study vaccines (each of the three consecutive production lots of the investigational influenza virus vaccine, the pooled influenza virus vaccine, and the comparator influenza vaccine).	3 weeks after vaccination
Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H1N1)	The percentage of subjects who were seroprotected and seroconverted were considered statistically compliant with the stated CBER guidance criteria if: the lower bound of the two-sided 95% CI for the percentage of seroprotected subjects (HI antibody titer ≥1:40) met or exceeded 70%.; the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion rate (prevaccination HI<10/ postvaccination HI ≥40 or at least a fourfold increase in titer from non-negative prevaccination serum [HI≥10]), for HI antibody met or exceeded 40%.	21 days after vaccination
Percentage of Subjects With Seroprotection and Seroconversion (Strain A/H3N2)	The percentage of subjects who were seroprotected and seroconverted were considered statistically compliant with the stated CBER guidance criteria if: the lower bound of the two-sided 95% CI for the percentage of seroprotected subjects (HI antibody titer ≥1:40) met or exceeded 70%.; the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion rate (prevaccination HI<10/ postvaccination HI ≥40 or at least a fourfold increase in titer from non-negative prevaccination serum [HI≥10]), for HI antibody met or exceeded 40%.	21 days after vaccination
Percentage of Subjects With Seroprotection and Seroconversion (Strain B)	The percentage of subjects who were seroprotected and seroconverted were considered statistically compliant with the stated CBER guidance criteria if: the lower bound of the two-sided 95% CI for the percentage of seroprotected subjects (HI antibody titer ≥1:40) met or exceeded 70%.; the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion rate (prevaccination HI<10/ postvaccination HI ≥40 or at least a fourfold increase in titer from non-negative prevaccination serum [HI≥10]), for HI antibody met or exceeded 40%.	21 days after vaccination

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: February 6, 2008
• First Submitted That Met QC Criteria: February 15, 2008
• First Posted (Estimate): February 18, 2008

Study Record Updates

• Last Update Posted (Estimate): May 8, 2012
• Last Update Submitted That Met QC Criteria: May 3, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Influenza; adults; different lots; trivalent subunit influenza virus vaccine (IVV); trivalent subunit influenza vaccine
• 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: V71P6; 13299