Inactivated Split Virus Seasonal Influenza Vaccine (Vero Cell-Derived)

Randomized, Age-stratified, Double Blind, Controlled Phase 3 Study Comparing a Vero Cell-derived Trivalent Seasonal Influenza Vaccine Made by the Modified Manufacturing Process With Vaccine Made by the Current Manufacturing Process and a Licensed Trivalent Influenza Vaccine in Healthy Adults Aged 18 Years and Older

The purpose of this study is to determine if a Vero cell-derived trivalent seasonal influenza vaccine produced by the modified manufacturing process:

1. induces immune responses comparable to that produced by the current manufacturing process
2. has an acceptable safety profile compared to a licensed trivalent seasonal influenza vaccine
3. demonstrates consistency of immune response among three different lots.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Vero cell-derived trivalent influenza vaccine manufactured with the modified manufacturing process (VCIV modified); Biological: VCIV manufactured with the current manufacturing process (VCIV current); Biological: Fluzone®, licensed trivalent influenza vaccine (TIV)

• Study Type: Interventional
• Enrollment (Actual): 1928
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • East Valley Family Physicians, PLC
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Paramount, California, United States, 90723
      • Center for Clinical Trials, LLC
    • San Diego, California, United States, 92103
      • California Research Foundation
    • San Francisco, California, United States, 94102
      • Benchmark Research San Francisco
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • Deland, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research, P.C.
    • St. Louis, Missouri, United States, 63141
      • Sundance Clinical Research, LLC
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research Inc.
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • PMG Research of Cary, LLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research, Inc.
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Texas
    • Austin, Texas, United States, 78705
      • Benchmark Research Austin
    • Fort Worth, Texas, United States, 76135
      • Benchmark Research
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Jean Brown Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant is 18 to 49 years of age, inclusive, at the time of screening (for Cohort 18 to 49 years of age);
• Participant is 50 years of age, inclusive, or older at the time of screening (for Cohort 50 years of age or older);
• Participant gave written informed consent prior to study entry
• Participant is generally healthy without any significant medical risk conditions, as determined by the Investigator's clinical judgment through collection of medical history and performance of a physical examination;
• Participant is willing and able to comply with the requirements of the protocol;
• Participant agrees to keep a record of symptoms for the duration of the study;

• If female and capable of bearing children - participant has a negative urine pregnancy test at the study site, within 36 hours prior to vaccination, and agrees to employ adequate birth control measures for the duration of the study. For the purposes of this study adequate birth control measures incorporate one of the following FDA approved birth control measures for the duration of the study:

  • Hormonal types of birth control (such as implants, birth control pills, patches or other methods) or an intrauterine device, OR
  • A barrier type of birth control measure (i.e., condoms, diaphragms, cervical caps, etc.).

Exclusion Criteria:

• Participant has been vaccinated with seasonal trivalent influenza vaccine in the current season;
• Participant has an oral temperature of ≥100.4°F (≥38.0°C) on the day of vaccination in this study;
• Participant has received a live vaccine within 4 weeks, or an inactivated or subunit vaccine within 2 weeks of study entry;
• Participant with a known history of infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBsAgs) or Hepatitis C Virus (HCV);
• Participant has any medically diagnosed or suspected immune deficient condition based on medical history and physical examination as determined by the Investigator;
• Participant has an immune compromising condition or disease, or is currently undergoing a form of treatment or was undergoing a form of treatment within 30 days prior to study entry that can be expected to influence immune response. Such treatment includes, but is not limited to, systemic or high dose inhaled corticosteroids (> 800 μg/day of beclomethasone dipropionate or equivalent), radiation treatment or other immunosuppressive or cytotoxic drugs (use of inhaled and nasal steroids will be permitted);
• Participant has a known history of Guillain Barré Syndrome, demyelinating disorders (including acute demyelinating encephalomyelitis (ADEM), Multiple Sclerosis) or convulsions;
• Participant has a history of severe allergic reactions or anaphylaxis as determined by the Investigator;
• Participant has a rash, dermatologic condition or tattoos which may interfere with injection site reaction rating as determined by the Investigator;
• Participant has received any blood products (e.g. blood transfusion or immunoglobulins) within 90 days prior to study entry;
• Participant has donated one or more units of blood (approximately 450 mL) or plasma within 30 days prior to study entry;
• Participant has a functional or surgical asplenia;
• Participant has a known or suspected problem with alcohol or drug abuse as determined by the Investigator;
• Participant is a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie., children, partner/spouse, siblings, parents) as well as employees of the Investigator or study site personnel conducting the study;
• If female, participant is pregnant or lactating at the time of study enrollment;
• Participant is currently enrolled or has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to study enrolment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study;
• Participant has any condition that in the opinion of the Investigator would interfere with evaluation of the vaccine or interpretation of study results.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VCIV - Modified manufacturing process (18-49 Years Old) Lot 1; Vero cell-derived trivalent influenza vaccine (VCIV)	Biological: Vero cell-derived trivalent influenza vaccine manufactured with the modified manufacturing process (VCIV modified)
Experimental: VCIV - Modified manufacturing process (18-49 Years Old) Lot 2; Vero cell-derived trivalent influenza vaccine (VCIV)	Biological: Vero cell-derived trivalent influenza vaccine manufactured with the modified manufacturing process (VCIV modified)
Experimental: VCIV - Modified manufacturing process (18-49 Years Old) Lot 3; Vero cell-derived trivalent influenza vaccine (VCIV)	Biological: Vero cell-derived trivalent influenza vaccine manufactured with the modified manufacturing process (VCIV modified)
Active Comparator: VCIV manufactured with current process (18-49 Years Old); Vero cell-derived trivalent influenza vaccine (VCIV)	Biological: VCIV manufactured with the current manufacturing process (VCIV current)
Active Comparator: Fluzone® (18-49 Years Old); Fluzone®, licensed trivalent influenza vaccine (TIV)	Biological: Fluzone®, licensed trivalent influenza vaccine (TIV)
Experimental: VCIV - Modified manufacturing process (≥50 Years Old) Lot 1; Vero cell-derived trivalent influenza vaccine (VCIV)	Biological: Vero cell-derived trivalent influenza vaccine manufactured with the modified manufacturing process (VCIV modified)
Experimental: VCIV - Modified manufacturing process (≥50 Years Old) Lot 2; Vero cell-derived trivalent influenza vaccine (VCIV)	Biological: Vero cell-derived trivalent influenza vaccine manufactured with the modified manufacturing process (VCIV modified)
Experimental: VCIV - Modified manufacturing process (≥50 Years Old) Lot 3; Vero cell-derived trivalent influenza vaccine (VCIV)	Biological: Vero cell-derived trivalent influenza vaccine manufactured with the modified manufacturing process (VCIV modified)
Active Comparator: Fluzone® (≥50 Years Old); Fluzone®, licensed trivalent influenza vaccine (TIV)	Biological: Fluzone®, licensed trivalent influenza vaccine (TIV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hemagglutination inhibition antibody (HIA) titer for each of the three antigens contained in the vaccine	21 days post-vaccination
Number of participants with fever	onset within 7 days post vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with seroprotective antibody titer [reciprocal HIA titer ≥40] for each of the three antigens contained in the vaccine		21 days post-vaccination
Number of participants demonstrating seroconversion to each of the three antigens contained in the vaccine	Seroconversion is defined as a ≥ 4-fold increase in HIA titer from baseline OR a reciprocal HIA titer ≥ 40 when there is no detectable HIA titer (reciprocal HIA titer < 10) at baseline	21 days post-vaccination
Fold increase of HIA titer for each of the three antigens contained in the vaccine as compared to baseline		21 days post-vaccination
Number of participants with solicited systemic reactions		within 7 days post-vaccination
Number of participants with injection site reactions		within 7 days post-vaccination
Frequency and severity of each solicited systemic reaction and injection site reaction		within 7 days of vaccination
Number of participants with adverse events		within 21 days post-vaccination
Frequency and severity of adverse events		within 21 days post-vaccination

Collaborators and Investigators

• Sponsor: Baxter Healthcare Corporation
• Investigators: Study Director: Nirjhar Chatterjee, MD, Baxter Healthcare Corporation

Publications and helpful links

General Publications

• StatXact 7 PROCs for SAS Users, Cytel Inc, Cambridge, 2005.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: January 17, 2013
• First Submitted That Met QC Criteria: January 22, 2013
• First Posted (Estimate): January 23, 2013

Study Record Updates

• Last Update Posted (Estimate): July 1, 2014
• Last Update Submitted That Met QC Criteria: June 27, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Active immunization against influenza disease
• 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: 721104