Safety and Immunogenicity Study of QIVc in Healthy Pediatric Subjects

A Phase 3, Randomized, Observer-Blind, Multicenter, Noninferiority Study to Evaluate Safety and Immunogenicity of a Cell-Based Quadrivalent Subunit Influenza Virus Vaccine (QIVc) and a United States Licensed Quadrivalent Influenza Virus Vaccine (QIV) in Healthy Subjects 6 Months Through 47 Months

This phase 3 clinical study is a randomized, observer-blind, comparator-controlled, multicenter study of QIVc versus a US-licensed comparator QIV in children 6 months through 47 months of age. The purpose of this study is to demonstrate that vaccination with QIVc elicits an immune response that is noninferior to that of a US-licensed comparator QIV containing the same virus strains, in children 6 months through 47 months of age.

Study Overview

• Status: Completed
• Conditions: Virus Diseases; Influenza; Human
• Intervention / Treatment: Biological: QIVc; Biological: Comparator QIV

• Study Type: Interventional
• Enrollment (Actual): 2414
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • 84035 CCR Research
  • California
    • Anaheim, California, United States, 92804
      • 84040 Southland Clnical Research Center
    • Downey, California, United States, 90240
      • 84044 Premier Health Research Center
    • Ontario, California, United States, 91763
      • 84028 Orange County Research Institute
    • Paramount, California, United States, 90723
      • 84029 Center for Clinical Trials
    • Sacramento, California, United States, 95864
      • 84012 Benchmark Research
    • San Diego, California, United States, 92123-1881
      • 84006 California Research Foundation
  • Florida
    • Miami, Florida, United States, 33142
      • 84001 Acevedo Clincal Research Associates
    • Opa-locka, Florida, United States, 33054
      • 84005 Sunshine Research Center
  • Georgia
    • Chamblee, Georgia, United States, 30341
      • 84052 Tekton Research
  • Idaho
    • Meridian, Idaho, United States, 83642
      • 84036 Advanced Clinical Research
  • Kansas
    • El Dorado, Kansas, United States, 67042
      • 84027 Heartland Research Associates
    • Newton, Kansas, United States, 67114
      • 84020 Heartland Research Associates
    • Wichita, Kansas, United States, 67205
      • 84014 Heartland Research Associates
    • Wichita, Kansas, United States, 67207
      • 84026 Heartland Research Associates
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • 84041 Kentucky Pediatric/ Adult Research
    • Louisville, Kentucky, United States, 40291
      • 84009 Bluegrass Clinical Research Inc.
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70806
      • 84008 Meridian Clinical Research
    • Haughton, Louisiana, United States, 71037
      • 84046 ACC Pediatric Research
    • Metairie, Louisiana, United States, 70006
      • 84004 Benchmark Research
    • Metairie, Louisiana, United States, 70006
      • 84022 Med Pharmics
  • Mississippi
    • Gulfport, Mississippi, United States, 39503
      • 84053 MedPharmics
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • 84051 Office of Craig A. Spiegel
    • Kansas City, Missouri, United States, 64114
      • 84016 Center for Pharmaceutical Research
  • Nebraska
    • Norfolk, Nebraska, United States, 68701
      • 84037 Meridian Clinical Research
    • Omaha, Nebraska, United States, 68116
      • 84017 Meridian Clinical Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • 84033 Med Pharmics
  • New York
    • Binghamton, New York, United States, 13901
      • 84013 Regional Clinical Research
  • Ohio
    • Dayton, Ohio, United States, 45406
      • 84045 Dayton Clinical
    • Dayton, Ohio, United States, 45419
      • 84003 PriMed Clinical Research
  • South Dakota
    • Dakota Dunes, South Dakota, United States, 57049
      • 84015 Meridian Clinical Research
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • 84032 Clinical Research Associates
  • Texas
    • Austin, Texas, United States, 78705
      • 84007 Benchmark Research
    • Fort Worth, Texas, United States, 76104
      • 84023 Ventavia Research Group
    • Fort Worth, Texas, United States, 76107
      • 84042 Universtiy of North Texas Health Science Center
    • Fort Worth, Texas, United States, 76135
      • 84043 Benchmark Research
    • Houston, Texas, United States, 77008
      • 84047 Ventavia Research Group
    • Houston, Texas, United States, 77055
      • 84011 West Houston Clinical Research
    • Keller, Texas, United States, 76248
      • 84019 Ventavia Research Group
    • San Angelo, Texas, United States, 76904
      • 84021 Benchmark Research
    • San Antonio, Texas, United States, 78240
      • 84002 Tekton Research
    • Tomball, Texas, United States, 77375
      • 84025 Pediatric Healthcare of NW Houston
  • Utah
    • Layton, Utah, United States, 84041
      • 84018 Tanner Clinic
    • Salt Lake City, Utah, United States, 84107
      • 84050 JBR Clinical Research Group
    • Salt Lake City, Utah, United States, 84121
      • 84048 J. Lewis Research/Foothill Family Clinic South
    • West Jordan, Utah, United States, 84088
      • 84031 Advanced Clinical Research
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • 84039 Pediatric Research of Charlottesville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 3 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Individuals of 6 through 47 months of age on the day of informed consent.
• Individuals whose parent(s)/Legally Acceptable Representative (LAR) have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
• Individuals who can comply with study procedures including follow-up
• Individual is in generally good health as per the Investigator's medical judgement

Exclusion Criteria:

• Acute (severe) febrile illness
• History of any anaphylaxis, serious vaccine reactions or hypersensitivity, including allergic reactions, to any component of vaccine or medical equipment whose use is foreseen in this study
• A known history of Guillain-Barre Syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis
• Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study
• Received influenza vaccination or has had documented influenza disease in the last 6 months prior to informed consent.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QIVc; Cell-derived Quadrivalent Influenza Vaccine containing 2 influenza type A strains and 2 influenza type B strains	Biological: QIVc; Previously vaccinated subjects received a 0.5 mL intramuscular dose of QIVc on Day 1; not previously vaccinated subjects received a 0.5 mL intramuscular dose of QIVc on Day 1 and Day 29.; Other Names: Flucelvax Quadrivalent
Active Comparator: Comparator QIV; Comparator Quadrivalent Influenza Vaccine containing 2 influenza type A strains and 2 influenza type B strains	Biological: Comparator QIV; Previously vaccinated subjects received a dose of Comparator QIV on Day 1; not previously vaccinated subjects received a dose of Comparator QIV on Day 1 and Day 29. Subjects 6 months through 35 months of age received a 0.25 mL intramuscular dose of Comparator QIV; subjects 36 months through 47 months of age received a 0.5 mL intramuscular dose of Comparator QIV.; Other Names: Afluria Quadrivalent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HAI) Assay Using Cell-derived Target Viruses	The GMT ratio is defined as the geometric mean of the postvaccination (28 days after last vaccination) HAI titer for the Comparator QIV divided by the geometric mean of the postvaccination HAI titer for QIVc.	Day 29 for previously vaccinated subjects; Day 57 for not previously vaccinated subjects
Immunogenicity Endpoint: Seroconversion Rates (SCR) and Differences in SCR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived Target Viruses	The SCR is defined as the percentage of subjects with either a prevaccination HAI titer <1:10 and a postvaccination HAI titer ≥1:40, or a prevaccination HAI titer ≥1:10 and a ≥4-fold increase in postvaccination HAI titer. The SCR difference is defined as the Comparator QIV SCR minus the QIVc SCR.	Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H3N2 Vaccine Strain by Microneutralization (MN) Assay Using Cell-derived Target Viruses	The GMT ratio is defined as the geometric mean of the postvaccination (28 days after last vaccination) MN titer for the Comparator QIV divided by the geometric mean of the postvaccination MN titer for QIVc.	Day 29 for previously vaccinated subjects; Day 57 for not previously vaccinated subjects
Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H3N2 Vaccine Strain by MN Assay Using Cell-derived Target Viruses	The SCR is defined as the percentage of subjects with either a prevaccination MN titer <1:10 and a postvaccination MN titer ≥1:40, or a prevaccination MN titer ≥1:10 and a ≥4-fold increase in postvaccination MN titer. The SCR difference is defined as the Comparator QIV SCR minus the QIVc SCR.	Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses	The GMT ratio is defined as the geometric mean of the postvaccination (28 days after last vaccination) HAI titer for the Comparator QIV divided by the geometric mean of the postvaccination HAI titer for QIVc.	Day 1 and Day 29 for previously vaccinated subjects; Day 1 and Day 57 for not previously vaccinated subjects
Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H1N1, B/Victoria and B/ Yamagata Vaccine Strains by HAI Assay Using Egg-derived Target Viruses	The SCR is defined as the percentage of subjects with either a prevaccination HAI titer <1:10 and a postvaccination HAI titer ≥1:40, or a prevaccination HAI titer ≥1:10 and a ≥4-fold increase in postvaccination HAI titer. The SCR difference is defined as the Comparator QIV SCR minus the QIVc SCR.	Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Immunogenicity Endpoint: GMT and GMT Ratio Against the A/H3N2 Vaccine Strain by MN Assay Using Egg-derived Target Viruses	The GMT ratio is defined as the geometric mean of the postvaccination (28 days after last vaccination) MN titer for the Comparator QIV divided by the geometric mean of the postvaccination MN titer for QIVc.	Day 1 and Day 29 for previously vaccinated subjects; Day 1 and Day 57 for not previously vaccinated subjects
Immunogenicity Endpoint: SCR and Difference in SCR Against the A/H3N2 Vaccine Strain by MN Assay Using Egg-derived Target Viruses	The SCR is defined as the percentage of subjects with either a prevaccination MN titer <1:10 and a postvaccination MN titer ≥1:40, or a prevaccination MN titer ≥1:10 and a ≥4-fold increase in postvaccination MN titer. The SCR difference is defined as the Comparator QIV SCR minus the QIVc SCR.	Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HAI Assay Using Cell-derived and Egg-derived Target Viruses	GMR is defined as the geometric mean of the (within-subject) fold increase in serum HAI GMT postvaccination (Day 29/57) compared to prevaccination (Day 1).	Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Immunogenicity Endpoint: GMR Against the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by MN Assay Using Cell-derived and Egg-derived Target Viruses	GMR is defined as the geometric mean of the (within-subject) fold increase in serum MN GMT postvaccination (Day 29/57) compared to prevaccination (Day 1).	Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Immunogenicity Endpoint: GMR Against the A/H3N2 Vaccine Strain by MN Assay Using Cell-derived and Egg-derived Target Viruses	GMR is defined as the geometric mean of the (within-subject) fold increase in serum MN GMT postvaccination (Day 29/57) compared to prevaccination (Day 1).	Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Safety Endpoint: Percentage of Subjects With Solicited Adverse Events (AEs)	The percentage of subjects with at least one solicited AE Day 1 through Day 7 after any study vaccination.	Day 1 to Day 7 after each vaccination (Day 1 to Day 7 for previously vaccinated subjects; Day 1 to Day 7 and Day 29 to Day 35 for not previously vaccinated subjects)
Safety Endpoint: Percentage of Subjects With Any Unsolicited AEs	The percentage of subjects with at least one unsolicited AE from Day 1 to Day 29 for previously vaccinated subjects and from Day 1 to Day 57 for not previously vaccinated subjects. Related AEs = considered at least possibly related to study vaccination by the investigator; Severity = based on the greatest severity associated with a preferred term for a reported AE.	Day 1 to Day 29 for previously vaccinated subjects; Day 1 to Day 57 for not previously vaccinated subjects
Safety Endpoint: Percentage of Subjects With Any Serious Adverse Events (SAEs), New Onset of Chronic Disease (NOCD) or AEs Leading to Withdrawal During the Entire Study Period	The percentage of subjects with any SAE, NOCD or AE leading to withdrawal during the study period from Day 1 to Day 181 for previously vaccinated subjects or from Day 1 to Day 209 for not previously vaccinated subjects. Definitions: SAEs = AEs defined as any untoward medical occurrence that at any dose resulted in one or more of the following: 1. Death, 2. Life-threatening 3. Required/prolonged hospitalization 4. Persistent or significant disability/incapacity 5. congenital anomaly/or birth defect 6. An important and significant medical event that may not be immediately life threatening or resulting in death or hospitalization but, based on appropriate medical judgment, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above	Day 1 to Day 181 for previously vaccinated subjects; Day 1 to Day 209 for not previously vaccinated subjects

Collaborators and Investigators

• Sponsor: Seqirus

Publications and helpful links

General Publications

• Essink BJ, Heeringa M, Jeanfreau RJ, Finn D, Matassa V, Edelman J, Hohenboken M, Molrine D. Safety and Immunogenicity of Cell-Based Quadrivalent Influenza Vaccine: A Randomized Trial. Pediatrics. 2022 Nov 1;150(5):e2022057509. doi: 10.1542/peds.2022-057509.

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2019
• Primary Completion (Actual): September 3, 2020
• Study Completion (Actual): September 3, 2020

Study Registration Dates

• First Submitted: August 27, 2019
• First Submitted That Met QC Criteria: August 27, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Actual): January 12, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Influenza; RNA Virus; WHO Strains
• Additional Relevant MeSH Terms: RNA Virus Infections; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Virus Diseases; Influenza, Human
• Other Study ID Numbers: V130_10; 2020-002785-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No