Study of Quadrivalent Influenza Vaccine Among Adults

Safety and Immunogenicity Trial Among Adults Administered Quadrivalent Influenza Vaccine

The aim of the study is to evaluate a prototype quadrivalent influenza vaccine (QIV), the licensed 2010-2011 trivalent influenza vaccine (TIV) containing the primary B strain, and the investigational TIV containing the alternate B strain in adult subjects.

Primary Objective:

• To demonstrate non-inferiority of antibody responses to QIV compared with licensed 2010-2011 TIV (containing the primary B strain) and investigational TIV (containing the alternate B strain) as assessed by geometric mean titer (GMT) ratios for each of the four virus strains separately among subjects 65 years of age and older

Observational Objective:

• To describe the safety profiles of TIV among subjects 18 years of age and older and QIV in subjects 65 years and older, as assessed by solicited injection site and systemic adverse events (AEs) collected for 7 days post-vaccination, unsolicited adverse events collected from 21 days post-vaccination, and adverse events of special interest and serious adverse events (SAEs) collected from Visit 1 to Visit 2.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Investigational Quadrivalent Inactivated Influenza Vaccine, No Preservative; Biological: Investigational Trivalent Inactivated Influenza Vaccine, No Preservative; Biological: Fluzone®: 2010-2011 Trivalent Inactivated Influenza Vaccine, No Preservative

Detailed Description

All participants will receive a single dose of their assigned vaccine during Visit 1. They will be followed up for safety and immunogenicity through Day 21 post-vaccination (Visit 2)

• Study Type: Interventional
• Enrollment (Actual): 739
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Hoover, Alabama, United States, 35216
  • Florida
    • South Miami, Florida, United States, 33143
  • Missouri
    • Springfield, Missouri, United States, 65802
  • New York
    • New York, New York, United States, 10004
    • Rochester, New York, United States, 14609
  • Ohio
    • Cincinnati, Ohio, United States, 45249
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18102
    • Bensalem, Pennsylvania, United States, 19020
  • Rhode Island
    • Warwick, Rhode Island, United States, 02866
  • South Carolina
    • Mt. Pleasant, South Carolina, United States, 29464
  • Tennessee
    • Nashville, Tennessee, United States, 37212
  • Texas
    • San Antonio, Texas, United States, 78229

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:

• Subject is 18 years of age or older on the day of inclusion.
• Informed consent form (ICF) has been signed and dated.
• Able to attend all scheduled visits and to comply with all trial procedures.
• For a woman of childbearing potential, use of an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks post-vaccination.

Exclusion criteria:

• Known pregnancy, or a positive urine pregnancy test.
• Currently breastfeeding a child.
• History of serious adverse reaction to any influenza vaccine.
• Receipt of any vaccine in the 4 weeks preceding the trial vaccination.
• Planned receipt of any vaccine between Visit 1 and Visit 2.
• Participation in another interventional clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first study vaccination or during the course of the study.
• Receipt of any influenza vaccine since 01 August 2010 (including 2009 H1N1 monovalent vaccine).
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances.
• Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response.
• Thrombocytopenia, bleeding disorder, or receipt of anticoagulants contraindicating intramuscular vaccination.
• Any condition that in the opinion of the Investigator would pose a health risk to the subject if enrolled or could interfere with the evaluation of the vaccine.
• Personal history of Guillain-Barré Syndrome (GBS).
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
• Any chronic illness that, in the opinion of the Investigator, is not well controlled or that may interfere with trial conduct or completion or with assessment of adverse events.
• Known seropositivity for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Current alcohol or drug use that, in the opinion of the Investigator, might interfere with the ability to comply with trial procedures.
• Identified as employees of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the employees or the Investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Investigational Quadrivalent Influenza Vaccine; Participants will receive a dose of Investigational Quadrivalent Inactivated Influenza Vaccine	Biological: Investigational Quadrivalent Inactivated Influenza Vaccine, No Preservative; 0.5 mL, Intramuscular
Experimental: Group 2: Investigational Trivalent Influenza Vaccine; Participants will receive a dose of Investigational Trivalent Inactivated Influenza Vaccine	Biological: Investigational Trivalent Inactivated Influenza Vaccine, No Preservative; 0.5 mL, Intramuscular
Active Comparator: Group 3: Licensed 2010-2011 Trivalent Influenza Vaccine; Participants will receive a dose of Licensed 2010-2011 Trivalent Inactivated Influenza Vaccine	Biological: Fluzone®: 2010-2011 Trivalent Inactivated Influenza Vaccine, No Preservative; 0.5 mL, Intramuscular; Other Names: Fluzone®
Active Comparator: Group 4: Licensed 2010-2011 Trivalent Influenza Vaccine; Participants will receive a dose of Licensed 2010-2011 Trivalent Inactivated Influenza Vaccine	Biological: Fluzone®: 2010-2011 Trivalent Inactivated Influenza Vaccine, No Preservative; 0.5 mL, Intramuscular; Other Names: Fluzone®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or With Trivalent Influenza Vaccines With Corresponding B Strain in Participants Aged 65 Years and Older.	Immunogenicity outcomes were assessed in serum samples by hemagglutination inhibition (HAI) assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as <10.	Day 21 post-vaccination
Geometric Mean Titers Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or After Trivalent Influenza Vaccines Without Corresponding B Strain in Participants Aged 65 Years and Older.	Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as <10.	Day 21 post-vaccination
Geometric Mean Titers Against the Influenza Virus Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines (TIV) in Participants Aged 18 Years or Older	Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as <10.	Day 0 and Day 21 post-vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or With Trivalent Influenza Vaccines (TIV) With Corresponding B Strains in Participants Aged 65 Years and Older.	Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as < 10. Seroconversion was defined as either a pre-vaccination HAI titer < 1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and ≥ four-fold increase in post-vaccination titer.	Day 21 post-vaccination
Seroconversion Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or With Trivalent Influenza Vaccines Without Corresponding B Strain in Participants Aged 65 Years and Older.	Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as <10. Seroconversion was defined as either a pre-vaccination HAI titer < 1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥ 1:10 and ≥ four-fold increase in post-vaccination titers.	Day 21 post-vaccination
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or With Trivalent Influenza Vaccines in Participants Aged 18 Years or Older.	Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as <10. Seroprotection was defined as a pre-vaccination and post-vaccination titer ≥ 1:40 (l/dil)	Day 21 post-vaccination
Seroconversion Against Influenza Virus Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or With Trivalent Influenza Vaccines in Participants Aged 18 Years and Older	Immunogenicity outcomes were assessed in serum samples by HAI assay. The lower limit of quantitation (LLOQ) was set at the lowest dilution used in the assay, 1/10. Titers below this level were reported as <10. Seroconversion was defined as either a pre-vaccination HAI titer <1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and ≥ four-fold increase in post-vaccination titer.	Day 21 post-vaccination
Number of Participants Reporting Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or With Trivalent Influenza Vaccines.	Solicited injection site reactions: Pain, Erythema and Swelling; Solicited systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 Injection site reactions: Pain - Significant; prevents daily activity; Erythema and Swelling >100 mm. Grade 3 solicited systemic reactions: Fever (Temperature) ≥102.1°F; Headache, Malaise, and Myalgia - Significant; prevents daily activity.	Day 0 up to day 21 post-vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: October 8, 2010
• First Submitted That Met QC Criteria: October 8, 2010
• First Posted (Estimate): October 11, 2010

Study Record Updates

• Last Update Posted (Estimate): October 23, 2013
• Last Update Submitted That Met QC Criteria: September 13, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Influenza; Trivalent Inactivated Influenza Vaccine; Quadrivalent Inactivated Influenza Vaccine; Influenza viruses
• 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: QIV03; UTN: U1111-1113-3619 (Other Identifier: WHO)