Safety and Immunogenicity Study of QIVc in Healthy Pediatric Subjects

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Influenza, Human, Virus Diseases

Intervention / Treatment
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* Biological: QIVc
* Biological: Comparator QIV


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 47 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QIVc<br>Cell-derived Quadrivalent Influenza Vaccine containing 2 influenza type A strains and 2 influenza type B strains | Biological: QIVc<br>* 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.<br>* Other names: Flucelvax Quadrivalent;|
| Active Comparator: Comparator QIV<br>Comparator Quadrivalent Influenza Vaccine containing 2 influenza type A strains and 2 influenza type B strains | Biological: Comparator QIV<br>* 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.<br>* Other names: Afluria Quadrivalent;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, RNA Virus, WHO Strains