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.

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 2016/2017 Quadrivalent Influenza Vaccine (comparator QIV) in a healthy pediatric population 6 months through 59 months 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 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

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: Seqirus Quadrivalent Inactivated Influenza Vaccine
* Biological: Comparator Quadrivalent Inactivated Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 59 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Seqirus QIV Cohort A<br>Seqirus Quadrivalent Inactivated Influenza Vaccine - Subjects 6 months through 35 months of age | Biological: 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 (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.<br>* Other names: Seqirus QIV;|
| Experimental: Seqirus QIV Cohort B<br>Seqirus Quadrivalent Inactivated Influenza Vaccine - Subjects 36 months through 59 months of age | Biological: 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 (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.<br>* Other names: Seqirus QIV;|
| Active Comparator: Comparator QIV Cohort A<br>Comparator Quadrivalent Inactivated Influenza Vaccine - Subjects 6 months through 35 months of age | Biological: Comparator Quadrivalent Inactivated Influenza Vaccine<br>* 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.<br>* Other names: Comparator QIV;|
| Active Comparator: Comparator QIV Cohort B<br>Comparator Quadrivalent Inactivated Influenza Vaccine - Subjects 36 months through 59 months of age | Biological: Comparator Quadrivalent Inactivated Influenza Vaccine<br>* 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.<br>* Other names: Comparator QIV;|

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 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) |