Study of Quadrivalent Influenza Vaccine Among Children

Safety and Immunogenicity Among Children 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 (B1), and the investigational TIV containing the alternate B (B2) strain in children.

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 children aged 6 months to less than 9 years of age

Secondary Objective:

To demonstrate superiority of antibody responses to each B strain in QIV compared with antibody titers following vaccination with the TIV that does not contain the corresponding B strain, as assessed by GMT ratios and seroconversion rates.

Observational Objective:

To describe the safety profile of QIV among subjects 6 months to less than 9 years of age, 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: Licensed 2010-2011 Trivalent Influenza Vaccine, No Preservative; Biological: Investigational Trivalent Influenza Vaccine with alternate B strain, No Preservative; Biological: Quadrivalent Influenza Vaccine, No Preservative

Detailed Description

Participants will receive a single dose of their assigned vaccine during Visit 1. For those requiring two doses of influenza vaccine, as per Advisory Committee on Immunization Practices (ACIP) guidance, a second dose of the assigned vaccine will be administered at Visit 2. All participants will be followed up for safety (up to 6 months post final vaccination) and for immunogenicity up to Day 28 post-vaccination (Visit 2 or Visit 3, as appropriate).

• Study Type: Interventional
• Enrollment (Actual): 4363
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
  • Arizona
    • Chandler, Arizona, United States, 85225
    • Chandler, Arizona, United States, 85224
    • Mesa, Arizona, United States, 85213
    • Mesa, Arizona, United States, 85203
    • Scottsdale, Arizona, United States, 85258
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • California
    • Los Angeles, California, United States, 90036
    • San Diego, California, United States, 92103
    • San Diego, California, United States, 92108
  • Colorado
    • Colorado Spring, Colorado, United States, 80922
    • Denver, Colorado, United States, 80239
  • Connecticut
    • Ridgefield, Connecticut, United States, 06877
  • Florida
    • Boca Raton, Florida, United States, 33432
    • Jacksonville, Florida, United States, 32216
    • Melbourne, Florida, United States, 32935
    • Miami Beach, Florida, United States, 33141
    • Ponte Vedra, Florida, United States, 32081
    • Sarasota, Florida, United States, 34239
    • Sarasota, Florida, United States, 34231
    • South Miami, Florida, United States, 33143
  • Georgia
    • Marietta, Georgia, United States, 30625
  • Kansas
    • Arkansas City, Kansas, United States, 67005
    • Newton, Kansas, United States, 67114
    • Overland Park, Kansas, United States, 66202
    • Wichita, Kansas, United States, 67207
    • Wichita, Kansas, United States, 67205
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
    • Crestview Hills, Kentucky, United States, 41017
    • Lexington, Kentucky, United States, 40509
  • Louisiana
    • Metairie, Louisiana, United States, 70006
  • Maryland
    • Columbia, Maryland, United States, 21045
  • Missouri
    • Kansas City, Missouri, United States, 64114
    • St. Louis, Missouri, United States, 63141
  • Nevada
    • Las Vegas, Nevada, United States, 89104
  • New York
    • Binghamton, New York, United States, 13901
  • North Carolina
    • Cary, North Carolina, United States, 27518
  • Ohio
    • Akron, Ohio, United States, 44311
    • Cleveland, Ohio, United States, 44121
    • Columbus, Ohio, United States, 43212
  • Oregon
    • Portland, Oregon, United States, 97203
  • Pennsylvania
    • Pittsburg, Pennsylvania, United States, 15220
    • Pittsburgh, Pennsylvania, United States, 15227
    • Scranton, Pennsylvania, United States, 18510
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
  • South Carolina
    • Barnwell, South Carolina, United States, 26812
    • Mount Pleasant, South Carolina, United States, 29464
  • Tennessee
    • Clarksville, Tennessee, United States, 37043
    • Kingsport, Tennessee, United States, 37664
  • Texas
    • Austin, Texas, United States, 78705
    • Fort Worth, Texas, United States, 76107
    • Ft. Worth, Texas, United States, 76135
    • Houston, Texas, United States, 77074
    • Katy, Texas, United States, 77450
  • Utah
    • Layton, Utah, United States, 84041
    • Murray, Utah, United States, 84107
    • Orem, Utah, United States, 84057
    • Provo, Utah, United States, 84604
    • Salt Lake City, Utah, United States, 84121
    • Salt Lake City, Utah, United States, 84109
    • Salt Lake City, Utah, United States, 84124
    • South Jordan, Utah, United States, 84095
    • West Jordan, Utah, United States, 84088
  • Virginia
    • Charlottesville, Virginia, United States, 22902
    • Midlothian, Virginia, United States, 23113
    • Williamsburg, Virginia, United States, 23185
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 8 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is 6 months to < 9 years of age on the day of inclusion.
• Parent/guardian is willing and able to attend scheduled visits and to comply with the study procedures during the entire duration of the study.
• Subject is in reasonably good health as assessed by the Investigator.
• Informed consent is granted by the parent(s) or other legally acceptable representative; assent by subjects 7 to < 9 years of age.
• For subjects 6 months to < 24 months of age, born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg (5.5 lbs).

Exclusion Criteria:

• History of allergy to egg proteins or any constituents of the vaccine.
• History of serious adverse reaction to any influenza vaccine.
• Any vaccination scheduled between Visit 1 and Visit 2 (or Visit 1 and Visit 3 for those requiring two doses).
• Receipt of any vaccine in the 4 weeks preceding the first study vaccination.
• 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.
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, 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.
• 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).
• Personal or immediate family history of congenital immune deficiency.
• Personal developmental delay, neurologic disorder, or seizure disorder.
• Any chronic illness that, in the opinion of the Investigator, is not well controlled and may interfere with trial conduct or completion, or with assessment of adverse events.
• Known seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C.
• Receipt of blood or blood-derived products (including immunoglobulin therapy) in the past 3 months, which might interfere with assessment of the immune response.
• 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 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: Licensed 2010-2011 TIV; Participants will receive the Licensed 2010-2011 Trivalent Influenza Vaccine containing the primary B strain.	Biological: Licensed 2010-2011 Trivalent Influenza Vaccine, No Preservative; 0.25 mL (6 to 35 months) or 0.5 mL (3 to <9 years), Intramuscular; Other Names: Fluzone®
Experimental: Group 2: Investigational TIV; Participants will receive the Investigational Trivalent Influenza Vaccine containing the alternate B strain	Biological: Investigational Trivalent Influenza Vaccine with alternate B strain, No Preservative; 0.25 mL (6 to 35 months) or 0.5 mL (3 to <9 years), Intramuscular
Experimental: Group 3: Investigational QIV; Participants will receive the investigational Quadrivalent Influenza Vaccine	Biological: Quadrivalent Influenza Vaccine, No Preservative; 0.25 mL (6 to 35 months), or 0.5 mL(3 to <9 years), Intramuscular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers Against Influenza A Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants	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 28 post final vaccination
Geometric Mean Titers Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines With Corresponding B Strain in All Participants	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 28 post final vaccination
Geometric Mean Titers Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Without Corresponding B Strain in All Participants	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 28 post final vaccination
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months.	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 28 post final vaccination
Geometric Mean Titers Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years.	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 28 post-vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines With Corresponding B Strain in All Participants	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	Day 28 post final vaccination
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants	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 ≥ 40 (l/dil)	Day 28 post final vaccination
Seroconversion Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants	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 a four-fold increase in post-vaccination.	Day 28 post final vaccination
Seroconversion Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Without Corresponding B Strain in All Participants.	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 a four-fold increase in post-vaccination.	Day 28 post final vaccination
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 6 Months to Less Than 36 Months.	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 ≥ 40 (l/dil).	Day 28 post final vaccination
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in Participants Aged 3 Years to Less Than 9 Years.	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 ≥ 40 (l/dil).	Day 28 post-vaccination
Seroprotection Against Influenza Vaccine Antigens After Vaccination With One Dose of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants	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 ≥ 40 (l/dil).	Day 28 post-vaccination
Seroprotection Against Influenza Vaccine Antigens After Vaccination With Two Doses of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants	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 ≥ 40 (l/dil).	Day 28 post final vaccination
Number of Participants Aged 6 Months to <36 Months Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines.	Solicited injection site reactions (Age 6-23 Months): Tenderness, Erythema and Swelling. Solicited systemic reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3: Tenderness: cries when injected limb is moved; Erythema and Swelling ≥ 50 mm; Fever: >103.1°F; Vomiting: ≥6 episodes/24 hours; Abnormal crying: >3 hours; Drowsiness: Sleeping most of the time; Loss of appetite: refuses ≥3 feeds/meals or most feeds/meals; Irritability: inconsolable. Solicited Injection site reactions (Age 24 Months to < 36 months): Pain, Erythema, and Swelling. Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3: Pain: Incapacitating, unable to perform usual activities; Redness and Swelling: ≥ 50 mm; Fever: ≥102.1°F; Headache, Malaise and Myalgia: Significant, prevents daily activity.	Day 0 up to Day 7 post-vaccination
Number of Participants Aged 3 Years to <9 Years Reporting Solicited Injection Site and Systemic Reactions Following Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines	Solicited injection site reactions: Pain, Redness, and Swelling. Solicited systemic reactions: Fever (Temperature); Headache, Malaise and Myalgia Grade 3 Pain: incapacitating, unable to perform usual activities; Redness and Swelling: ≥ 50 mm; Fever: ≥ 102.1°F; Headache, Malaise and Myalgia: Significant, prevents daily activity, respectively.	Day 0 up to Day 7 post-vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Greenberg DP, Robertson CA, Landolfi VA, Bhaumik A, Senders SD, Decker MD. Safety and immunogenicity of an inactivated quadrivalent influenza vaccine in children 6 months through 8 years of age. Pediatr Infect Dis J. 2014 Jun;33(6):630-6. doi: 10.1097/INF.0000000000000254.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: November 11, 2010
• First Submitted That Met QC Criteria: November 11, 2010
• First Posted (Estimate): November 15, 2010

Study Record Updates

• Last Update Posted (Estimate): July 14, 2015
• Last Update Submitted That Met QC Criteria: June 16, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Influenza; Fluzone®; Quadrivalent Influenza Vaccine; Trivalent 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: QIV04; UTN: U1111-1114-3713 (Other Identifier: WHO)