Study of Quadrivalent Influenza Vaccine Among Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT01240746
First received: November 11, 2010
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Influenza
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
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity Among Children Administered Quadrivalent Influenza Vaccine

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Geometric Mean Titers Against Influenza A Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants [ Time Frame: Day 28 post final vaccination ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 28 post final vaccination ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 28 post final vaccination ] [ Designated as safety issue: No ]
    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.

  • 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. [ Time Frame: Day 28 post final vaccination ] [ Designated as safety issue: No ]
    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.

  • 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. [ Time Frame: Day 28 post-vaccination ] [ Designated as safety issue: No ]
    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:
  • Seroconversion Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines With Corresponding B Strain in All Participants [ Time Frame: Day 28 post final vaccination ] [ Designated as safety issue: No ]

    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


  • Seroprotection Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants [ Time Frame: Day 28 post final vaccination ] [ Designated as safety issue: No ]

    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)


  • Seroconversion Against Influenza Vaccine Antigens After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants [ Time Frame: Day 28 post final vaccination ] [ Designated as safety issue: No ]

    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.


  • Seroconversion Against Influenza B Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines Without Corresponding B Strain in All Participants. [ Time Frame: Day 28 post final vaccination ] [ Designated as safety issue: No ]

    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.


  • 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. [ Time Frame: Day 28 post final vaccination ] [ Designated as safety issue: No ]

    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).


  • 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. [ Time Frame: Day 28 post-vaccination ] [ Designated as safety issue: No ]

    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).


  • Seroprotection Against Influenza Vaccine Antigens After Vaccination With One Dose of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants [ Time Frame: Day 28 post-vaccination ] [ Designated as safety issue: No ]

    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).


  • Seroprotection Against Influenza Vaccine Antigens After Vaccination With Two Doses of Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants [ Time Frame: Day 28 post final vaccination ] [ Designated as safety issue: No ]

    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).


  • 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. [ Time Frame: Day 0 up to Day 7 post-vaccination ] [ Designated as safety issue: No ]

    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.


  • 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 [ Time Frame: Day 0 up to Day 7 post-vaccination ] [ Designated as safety issue: No ]
    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.


Enrollment: 4363
Study Start Date: November 2010
Study Completion Date: February 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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).

  Eligibility

Ages Eligible for Study:   6 Months to 8 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01240746

  Show 67 Study Locations
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Investigators
Study Director: Medical Director Sanofi Pasteur Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01240746     History of Changes
Other Study ID Numbers: QIV04, UTN: U1111-1114-3713
Study First Received: November 11, 2010
Results First Received: July 3, 2013
Last Updated: December 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Influenza
Quadrivalent Influenza Vaccine
Trivalent Influenza Vaccine
Influenza viruses
Fluzone®

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
Respiratory Tract Diseases
Respiratory Tract Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 29, 2014