A Study to Evaluate the Immunogenicity and Safety of Seqirus Quadrivalent Influenza Vaccine (QIV) in a Pediatric Population 6 Months Through 59 Months of Age.

A Phase 3, Randomized, Multicenter, Observer-blinded, Noninferiority Study to Evaluate the Immunogenicity and Safety of a Quadrivalent Inactivated Influenza Virus Vaccine (Seqirus QIV) With a US-licensed Quadrivalent Inactivated Comparator Influenza Virus Vaccine (Comparator QIV) in a Pediatric Population 6 Months Through 59 Months of Age

This is a study to assess the immune (antibody) response and safety of a Seqirus split virion, inactivated Quadrivalent Influenza Vaccine (Seqirus QIV), in comparison with a US licensed 2016/2017 Quadrivalent Influenza Vaccine (comparator QIV) in a healthy pediatric population 6 months through 59 months of age.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Biological: Seqirus Quadrivalent Inactivated Influenza Vaccine; Biological: Comparator Quadrivalent Inactivated Influenza Vaccine

• Study Type: Interventional
• Enrollment (Actual): 2250
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Site 434
    • Mobile, Alabama, United States, 36608
      • Site 442
  • California
    • Anaheim, California, United States, 92804
      • Site 430
    • Anaheim, California, United States, 92804
      • Site 437
    • Downey, California, United States, 90241
      • Site 423
    • Ontario, California, United States, 91762
      • Site 397
    • Paramount, California, United States, 90723
      • Site 445
    • Sacramento, California, United States, 95822
      • Site 402
    • San Diego, California, United States, 92103
      • Site 425
  • Florida
    • Miami, Florida, United States, 33175
      • Site 418
    • Miami, Florida, United States, 33176
      • Site 426
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Site 289
  • Kansas
    • Augusta, Kansas, United States, 67010
      • Site 390
    • Newton, Kansas, United States, 67114
      • Site 421
    • Wichita, Kansas, United States, 67205
      • Site 422
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Site 443
    • Louisville, Kentucky, United States, 40291
      • Site 420
    • Louisville, Kentucky, United States, 40291
      • Site 441
  • Louisiana
    • Metairie, Louisiana, United States, 70002
      • Site 393
    • Metairie, Louisiana, United States, 70006
      • Site 436
  • New York
    • Binghamton, New York, United States, 13901
      • Site 285
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Site 429
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Site 446
    • Dayton, Ohio, United States, 45419
      • Site 427
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Site 419
    • Spartanburg, South Carolina, United States, 29303
      • Site 439
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Site 308
    • Kingsport, Tennessee, United States, 37660
      • Site 444
  • Texas
    • Austin, Texas, United States, 78705
      • Site 283
    • Fort Worth, Texas, United States, 76135
      • Site 282
    • San Angelo, Texas, United States, 76904
      • Site 288
  • Utah
    • Layton, Utah, United States, 84041
      • Site 395
    • Salt Lake City, Utah, United States, 84109
      • Site 431
    • Salt Lake City, Utah, United States, 84121
      • Site 424
    • Salt Lake City, Utah, United States, 84124
      • Site 428
    • West Jordan, Utah, United States, 84084
      • Site 440
    • West Jordan, Utah, United States, 84088
      • Site 433
    • West Jordan, Utah, United States, 84088
      • Site 435
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • Site 438

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subject 6 months through to 59 months of age at the time of first vaccination and born between 36 and 42 weeks of gestation;
• Parent or legally acceptable representative able to provide written informed consent and be willing and able to adhere to all protocol requirements including blood draws.
• Subject is in generally good health as per the Investigator's medical judgment

Exclusion Criteria:

• History of allergic reactions to egg proteins or any components of the Study Vaccines;
• History of serious adverse reactions to any influenza vaccines;
• History of Guillain-Barré syndrome or other demyelinating disease such as encephalomyelitis and transverse myelitis;
• History of licensed or investigational influenza vaccination in the last 6 months;
• Clinical signs of active infection and/or an axillary temperature of ≥ 99.5°F / (≥ 37.5 °C) on the day of vaccination or within 48 hours preceding vaccination.
• Current or recent, acute or chronic medical conditions that in the opinion of the Investigator are clinically significant and/or unstable
• History of any seizures, with the exception of a single febrile seizure;
• Self-reported or known seropositivity suggestive of acute or chronic viral infection for human immunodeficiency virus, hepatitis B or hepatitis C;
• Known or suspected congenital or acquired immunosuppressive conditions;
• Current or recent immunosuppressive or immunomodulatory therapy
• Current or medical history of malignant neoplasms;
• Administration of immunoglobulin and/or any blood products within the previous 90 days preceding the administration of the Study Vaccine or planned administration during the study;
• Participation in a clinical trial or use of an investigational compound within 28 days prior to or 28 days after receiving the Study Vaccine, or plans to enter a study during this period;
• Vaccination with a licensed vaccine 21 days (for live or inactivated vaccines) prior to receiving the Study Vaccine, or plans to receive any licensed vaccine prior to the Study Exit Visit.
• Medical conditions or treatment contraindicating intramuscular vaccination due to increased risk of bleeding.
• Family members of the employees of the Investigator or study center with direct involvement in the study, or with other clinical studies under the direction of that Investigator or study center.

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: Seqirus QIV Cohort A; Seqirus Quadrivalent Inactivated Influenza Vaccine - Subjects 6 months through 35 months of age	Biological: Seqirus Quadrivalent Inactivated Influenza Vaccine; The Seqirus study vaccine is a sterile, thimerosal-free suspension containing 60 mcg total hemagglutinin antigen per 0.5 mL (15 mcg each of the four recommended influenza strains for the Northern Hemisphere 2016/2017 influenza season). Subjects will receive one or two doses according to the recommendations of the Advisory Committee on Immunization Practices for the United States 2016-17 Influenza Season. Preferred sites for intramuscular injection are the anterolateral aspect of the thigh in infants 6 months through 11 months of age, the anterolateral aspect of the thigh (or the deltoid muscle of the arm if muscle mass is adequate) in children 12 months through 35 months of age.; Other Names: Seqirus QIV
Experimental: Seqirus QIV Cohort B; Seqirus Quadrivalent Inactivated Influenza Vaccine - Subjects 36 months through 59 months of age	Biological: Seqirus Quadrivalent Inactivated Influenza Vaccine; The Seqirus study vaccine is a sterile, thimerosal-free suspension containing 60 mcg total hemagglutinin antigen per 0.5 mL (15 mcg each of the four recommended influenza strains for the Northern Hemisphere 2016/2017 influenza season). Subjects will receive one or two doses according to the recommendations of the Advisory Committee on Immunization Practices for the United States 2016-17 Influenza Season. Preferred sites for intramuscular injection are the anterolateral aspect of the thigh in infants 6 months through 11 months of age, the anterolateral aspect of the thigh (or the deltoid muscle of the arm if muscle mass is adequate) in children 12 months through 35 months of age.; Other Names: Seqirus QIV
Active Comparator: Comparator QIV Cohort A; Comparator Quadrivalent Inactivated Influenza Vaccine - Subjects 6 months through 35 months of age	Biological: Comparator Quadrivalent Inactivated Influenza Vaccine; The comparator Quadrivalent Inactivated Influenza vaccine is a US-licensed product containing four recommended influenza strains for the Northern Hemisphere 2016/2017 influenza season. Subjects will receive one or two doses according to the recommendations of the Advisory Committee on Immunization Practices for the United States 2016-17 Influenza Season. Preferred sites for intramuscular injection of the non-dominant arm in children 36 months through 59 months of age.; Other Names: Comparator QIV
Active Comparator: Comparator QIV Cohort B; Comparator Quadrivalent Inactivated Influenza Vaccine - Subjects 36 months through 59 months of age	Biological: Comparator Quadrivalent Inactivated Influenza Vaccine; The comparator Quadrivalent Inactivated Influenza vaccine is a US-licensed product containing four recommended influenza strains for the Northern Hemisphere 2016/2017 influenza season. Subjects will receive one or two doses according to the recommendations of the Advisory Committee on Immunization Practices for the United States 2016-17 Influenza Season. Preferred sites for intramuscular injection of the non-dominant arm in children 36 months through 59 months of age.; Other Names: Comparator QIV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Geometric Mean Titer (GMT) Ratio of Each Virus Strain.	Noninferiority of Seqirus QIV compared to comparator QIV was assessed by hemagglutination inhibition (HI) antibody geometric mean titer (GMT) for each viral strain included in the vaccines. The GMT ratio is defined as the geometric mean of the postvaccination HI titer for the US-licensed comparator QIV over the geometric mean of the postvaccination HI titer for Seqirus QIV. B/VIC = B/Victoria B/YAM = B/Yamagata	Postvaccination (28 days after last vaccination)
The Difference in Seroconversion Rate (SCR) for Each Virus Strain.	Noninferiority of Seqirus QIV compared to comparator QIV will be assessed by seroconversion rate (SCR) for each viral strain. SCR is defined as the percentage of subjects with either a prevaccination HI titer < 1:10 and a postvaccination HI titer ≥ 1:40, or a prevaccination HI titer ≥ 1:10 and a ≥ 4-fold increase in postvaccination HI titer. For the SCR comparison, the difference between the SCR for each vaccine (for each strain) will be determined.	Postvaccination (28 days after last vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Solicited Local Adverse Reactions and Solicited Systemic Adverse Events (AE)	Frequency and severity of solicited local adverse reactions and systemic AEs for 7 days after each vaccination dose	Postvaccination (up to 7 days after vaccination)
Number of Participants With Cellulitis-like Reactions	Frequency of cellulitis-like reactions for at least 28 days after each vaccination dose	Postvaccination (up to 28 days after each vaccination)
Number of Participants With Unsolicited AEs	Frequency and severity of unsolicited AEs for at least 28 days after each vaccination dose	Postvaccination (up to 28 days after vaccination)
Number of Participants With Serious Adverse Events (SAE)	Frequency of SAEs for 180 days after the last vaccination dose. SAE = serious adverse events, AESI = adverse event of special interest	180 days after the last vaccination dose.
Geometric Mean of Hemagglutination Titers (HI GMTs) Prevaccination (Day 1) and Postvaccination (Study Exit Visit) of Each Virus Strain	The humoral immune response will be assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains will be used to calculate geometric mean of HI titers prevaccination & postvaccination.	28 days after last vaccination.
Seroconversion Rates (SCRs) of Each Virus Strain	The humoral immune response will be assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains will be used to calculate SCRs defined as the % of subjects with either a prevaccination HI titer < 1:10 and a postvaccination HI titer ≥ 1:40 or a prevaccination titer ≥ 1:10 and a ≥ 4-fold increase in postvaccination titer.	28 days after last vaccination
Seroprotection Rates of Each Virus Strain	The humoral immune response will be assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains will be used to calculate the percentage of subjects with a titer ≥40 (seroprotection rates) at Day 1 and at Study Exit Visit.	28 days after last vaccination.
Geometric Mean Fold Increase (GMFI) of Each Virus Strain	The humoral immune response will be assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains will be used to calculate GMFIs, defined as the geometric mean fold titer change (rise) from Day 1 to Study Exit Visit.	Prevaccination (Day 1) and Postvaccination (28 days after last vaccination)

Collaborators and Investigators

• Sponsor: Seqirus

Publications and helpful links

General Publications

• Statler VA, Albano FR, Airey J, Sawlwin DC, Graves Jones A, Matassa V, Heijnen E, Edelman J, Marshall GS. Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in children 6-59 months of age: A phase 3, randomized, noninferiority study. Vaccine. 2019 Jan 7;37(2):343-351. doi: 10.1016/j.vaccine.2018.07.036. Epub 2018 Jul 26.

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2016
• Primary Completion (Actual): March 9, 2017
• Study Completion (Actual): August 11, 2017

Study Registration Dates

• First Submitted: September 22, 2016
• First Submitted That Met QC Criteria: September 22, 2016
• First Posted (Estimate): September 26, 2016

Study Record Updates

• Last Update Posted (Actual): January 23, 2019
• Last Update Submitted That Met QC Criteria: December 30, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• 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: CSLCT-QIV-15-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided