Study of Quadrivalent Influenza Vaccine Among Adults

• ClinicalTrials.gov Identifier: NCT01218646
• Recruitment Status: Completed
• First Posted: October 11, 2010
• Results First Posted: September 12, 2013
• Last Update Posted: October 23, 2013
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Influenza	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	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 739 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity Trial Among Adults Administered Quadrivalent Influenza Vaccine
• Study Start Date: October 2010
• Actual Primary Completion Date: March 2011
• Actual Study Completion Date: April 2011

Arms and Interventions

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 Name: 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 Name: Fluzone®

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: Day 21 post-vaccination ]
   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.
2. 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. [ Time Frame: Day 21 post-vaccination ]
   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.
3. 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 [ Time Frame: Day 0 and Day 21 post-vaccination ]
   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.

Other Outcome Measures:

1. 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. [ Time Frame: Day 21 post-vaccination ]

   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.

2. 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. [ Time Frame: Day 21 post-vaccination ]

   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.

3. Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or With Trivalent Influenza Vaccines in Participants Aged 18 Years or Older. [ Time Frame: Day 21 post-vaccination ]

   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)

4. Seroconversion Against Influenza Virus Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or With Trivalent Influenza Vaccines in Participants Aged 18 Years and Older [ Time Frame: Day 21 post-vaccination ]

   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.

5. Number of Participants Reporting Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or With Trivalent Influenza Vaccines. [ Time Frame: Day 0 up to day 21 post-vaccination ]

   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

Hoover, Alabama, United States, 35216

United States, Florida

South Miami, Florida, United States, 33143

United States, Missouri

Springfield, Missouri, United States, 65802

United States, New York

New York, New York, United States, 10004

Rochester, New York, United States, 14609

United States, Ohio

Cincinnati, Ohio, United States, 45249

United States, Pennsylvania

Allentown, Pennsylvania, United States, 18102

Bensalem, Pennsylvania, United States, 19020

United States, Rhode Island

Warwick, Rhode Island, United States, 02866

United States, South Carolina

Mt. Pleasant, South Carolina, United States, 29464

United States, Tennessee

Nashville, Tennessee, United States, 37212

United States, Texas

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director; Sanofi Pasteur Inc.

More Information

Additional Information:

Related Info 

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01218646
• Other Study ID Numbers: QIV03; UTN: U1111-1113-3619 ( Other Identifier: WHO )
• First Posted: October 11, 2010
• Results First Posted: September 12, 2013
• Last Update Posted: October 23, 2013
• Last Verified: September 2013

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Influenza; Quadrivalent Inactivated Influenza Vaccine; Trivalent Inactivated Influenza Vaccine; Influenza viruses

Additional relevant MeSH terms:

Influenza, Human; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs