A Study to Evaluate the Immunogenicity and Safety of Seqirus Quadrivalent Influenza Vaccine (QIV) in a Pediatric Population 5 Through 17 Years of Age

Study Overview
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Brief Summary
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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 2015/2016 Quadrivalent Influenza Vaccine (comparator QIV) in a healthy pediatric population 5 through 17 years of age.

Official Title
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A Phase 3, Randomized, Multicenter, Observer-Blinded, Noninferiority Study to Evaluate the Immunogenicity and Safety of a Seqirus Quadrivalent Inactivated Influenza Virus Vaccine (Seqirus QIV) With a US-Licensed 2015-2016 Quadrivalent Inactivated Comparator Influenza Vaccine (Comparator QIV) in a Pediatric Population 5 Through 17 Years of Age

Conditions
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Influenza, Human

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females 5 through 17 years of age on the day of first study vaccination. 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. Participant assent will also be obtained if required. If applicable, females of childbearing potential (ie, ovulating, not surgically sterile) must be abstinent or be willing to use a medically accepted contraceptive regimen until at least 28 days after the last Study Vaccine. Females of childbearing potential must return a negative urine pregnancy test result, prior to any vaccination dose with the Study Vaccine. 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. History of licensed or investigational influenza vaccination in the last 6 months. Clinical signs of active infection and/or an oral temperature of ≥ 100°F (37.8°C) on the day of planned Study Vaccine administration 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 (such as illness exacerbations) within the preceding 30 days. 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, as follows: Chronic or long-term systemic corticosteroids: ≥ 0.125 mg/kg/day of oral prednisolone or equivalent daily; Sporadic systemic corticosteroids: ≥ 0.5 mg/kg/day of oral prednisolone or equivalent for two or more short courses of > 3 days in the 3 months preceding vaccination; Antineoplastic chemotherapy or radiation therapy within the 6 months preceding vaccination. Note: Use of topical, inhalant or localised tissue injections of corticosteroids prior to administration of the Study Vaccine or throughout the study are acceptable. Administration of immunoglobulin and/or any blood products within the 3 months preceding vaccination, or planned administration during the study. Participation in a clinical trial or use of an investigational compound within 28 days prior to the first dose of Study Vaccine, or within 28 days after receiving the final indicated dose of Study Vaccine, or plans to enter a study during this period. Vaccination with a licensed vaccine 28 days (for live or inactivated vaccines) prior to receiving the first dose of Study Vaccine, or plans to receive any licensed vaccine prior to the Study Exit Visit. Pregnant or lactating females.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Seqirus Quadrivalent Inactivated Influenza Vaccine<br>The Seqirus study vaccine is a sterile, thimerosal-free suspension containing 60 mcg total hemagglutinin antigen per 0.5 mL dose (15 mcg each of the four recommended influenza strains for the Northern Hemisphere 2015/2016 influenza season). | Biological: Seqirus QIV<br>* Seqirus QIV, inactivated, split-virion, thimerosal-free, quadrivalent influenza vaccine, administered as a 0.5 mL intramuscular dose. The vaccine is presented in a prefilled needleless syringe. The subject's age and influenza vaccination history determines the dosing regimen (a single vaccination or a 2-vaccination regimen administered 28 days apart) according to the most recent US ACIP guidelines for seasonal influenza vaccination.<br>|
| Active Comparator: Comparator Quadrivalent Influenza Vaccine<br>The comparator Quadrivalent Inactivated Influenza vaccine is a US-licensed product containing four recommended influenza strains for the Northern Hemisphere 2015/2016 influenza season. | Biological: Comparator QIV<br>* The US-licensed Comparator QIV, inactivated, split-virion, thimerosal-free, quadrivalent influenza vaccine, administered as a 0.5 mL intramuscular dose. The vaccine is presented in a prefilled needleless syringe. The subject's age and influenza vaccination history determines the dosing regimen (a single vaccination or a 2-vaccination regimen administered 28 days apart) according to the most recent US ACIP guidelines for seasonal influenza vaccination.<br>* Other names: Fluarix Quadrivalent;|

What is the study measuring?
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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 the eight co-primary endpoints of hemagglutination inhibition (HI) antibody geometric mean titer (GMT) and seroconversion rate (SCR) 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. | 28 days after last vaccination. | 
| The Difference in Seroconversion Rate (SCR) for Each Virus Strain. | Noninferiority of Seqirus QIV compared to Comparator QIV was assessed by the eight co-primary endpoints of HI geometric mean titer (GMT) and seroconversion rate (SCR) for each viral strain. The rate of 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 virus strain will be determined. | 28 days after last vaccination. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoint: The Frequency and Severity of Solicited Local Adverse Reactions. | Frequency and severity of solicited local adverse reactions (AEs) for 7 days (ie, day of vaccination and 6 subsequent days) after each vaccination dose | 7 days after each vaccination. | 
| Safety Endpoint: The Frequency and Severity of Solicited Systemic Adverse Events (AEs). | Frequency and severity of solicited systemic adverse events (AEs) for 7 days (ie, day of vaccination and 6 subsequent days) after each vaccination dose | 7 days after each vaccination. | 
| Safety Endpoint: The Frequency of Cellulitis-like Reaction. | Frequency of cellulitis-like reaction for at least 28 days after each vaccination dose | 28 days after each vaccination. | 
| Safety Endpoint: The Frequency and Severity of Unsolicited Adverse Events (AEs). | Frequency and severity of unsolicited AEs for at least 28 days (ie, day of vaccination and 27 subsequent days) after each vaccination dose | 28 days after each vaccination. | 
| Safety Endpoint: The Frequency of Serious Adverse Events (SAEs). | Frequency of serious adverse events (SAEs) for 180 days after the last vaccination dose. | 180 days after the last vaccination dose. | 
| Immunogenicity Endpoint: GMTs - Geometric Mean of HI Titers Prevaccination (Day 1) and Postvaccination (Study Exit Visit) | The humoral immune response was assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains was used to calculate: - Geometric mean of HI titers prevaccination & postvaccination | 28 days after last vaccination. | 
| Immunogenicity Endpoint: Seroconversion Rate (SCR) | The humoral immune response was assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains was used to calculate: - SCRs: % 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. | 
| Immunogenicity Endpoint: Seroprotection Rate | The humoral immune response was assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains was used to calculate: - The % of subjects with a titer ≥40 (seroprotection rates) at Day 1 and at Exit Visit | 28 days after last vaccination. | 
| Immunogenicity Endpoint: Geometric Mean Fold Increase (GMFI) | The humoral immune response was assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains was used to calculate: - Geometric mean fold increase (GMFI): geometric mean fold titer rise from Day 1 to Exit Visit | 28 days after last vaccination. |