A Study to Evaluate the Safety and Tolerability of Trivalent Influenza Virus Vaccine in Children Aged 5 Years to < 9 Years

Study Overview
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Brief Summary
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This is a study to assess the safety of a bioCSL split virion, inactivated Trivalent Influenza Virus vaccine containing the 2014/2015 Northern Hemisphere strains of vaccine in children aged 5 years to less than 9 years. Comparison will be made to a licensed Quadrivalent Influenza Virus vaccine that complies with the FDA recommendations for the 2014/2015 influenza season in the US.

Official Title
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A Phase IV, Multicenter, Randomized, Observer-blind, Parallel-arm Study to Evaluate the Safety and Tolerability of CSL's Trivalent Influenza Virus Vaccine (CSL TIV) in Children 5 to Less Than 9 Years of Age.

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: bioCSL Trivalent Influenza Virus Vaccine (CSL TIV)
* Biological: Comparator Quadrivalent Influenza Virus Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged 5 to less than 9 years at the time of first study vaccination. The subject's parent or guardian to provide written informed consent and be willing and able to adhere to all protocol requirements. In good health, as determined by medical history and a targeted physical examination (if warranted). Exclusion Criteria: Known hypersensitivity to a previous dose of Influenza Virus Vaccine or allergy to eggs or any components of the study vaccines. Clinical signs of significant active infection or an elevated oral temperature at study entry. A clinically significant medical or psychiatric condition. A history of seizures or febrile convulsions or Guillain-Barré syndrome. Vaccination with a seasonal or experimental influenza virus vaccine in the 6 months preceding study entry. Vaccination with a licensed vaccine within 14 days preceding study entry, or planning to be vaccinated with another licensed vaccine before the study exit evaluation. Currently receiving systemic glucocorticoid therapy (excluding intra-articular, topical or inhaled preparations) or have received such therapy within the 3 months preceding study entry. Currently receiving immunoglobulins and/or any blood products or have received such treatment within the 3 months preceding the administration of the study vaccine. Currently receiving treatment with warfarin or other anticoagulants.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 8 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bioCSL Trivalent Influenza Virus Vaccine (CSL TIV)<br>The bioCSL study vaccine is a sterile, thiomersal-free suspension containing 45 mcg total haemagglutinin antigen per 0.5 mL dose (15 mcg each of the three recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season). | Biological: bioCSL Trivalent Influenza Virus Vaccine (CSL TIV)<br>* Subjects will receive one or two study vaccinations depending on their influenza vaccine history. The vaccine will be administered by intramuscular injection.<br>|
| Active Comparator: Comparator Quadrivalent Influenza Virus Vaccine<br>The comparator vaccine is a US-licensed product containing four recommended influenza strains for the Northern Hemisphere 2014/2015 influenza season. | Biological: Comparator Quadrivalent Influenza Virus Vaccine<br>* Subjects will receive one or two study vaccinations depending on their influenza vaccine history. The vaccine will be administered by intramuscular injection.<br>* Other names: Fluzone Quadrivalent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Frequency and Intensity of Fever Events Occurring During the 7 Days After Each Administration of CSL TIV Vaccine. | The overall percentage of subjects reporting at least one fever event after administration of bioCSL TIV. A fever event was defined as an oral temperature ≥ 38°C (≥ 100.4°F). The intensity was calculated as follows: • Mild: ≥ 100.4 to < 101.3°F (≥ 38.0 to < 38.5°C) • Moderate: ≥ 101.3 to < 102.2°F (≥ 38.5 to < 39.0°C) • Severe: ≥ 102.2°F (≥ 39.0°C) | 7 days after each administration of vaccine. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Frequency and Intensity of Fever Events Occurring During the 7 Days After Each Administration of the Comparator Influenza Virus Vaccine. | The overall percentage of subjects reporting at least one fever event after administration of the comparator influenza virus vaccine. A fever event was defined as an oral temperature ≥ 38°C (≥ 100.4°F). The intensity was calculated as follows: • Mild: ≥ 100.4 to < 101.3°F (≥ 38.0 to < 38.5°C) • Moderate: ≥ 101.3 to < 102.2°F (≥ 38.5 to < 39.0°C) • Severe: ≥ 102.2°F (≥ 39.0°C). | 7 days after each administration of vaccine. | 
| The Frequency and Intensity of Vaccine-related Fever Events Occurring During the 7 Days After Each Administration of CSL TIV Vaccine or Comparator Influenza Virus Vaccine. | Percentage of subjects with a related fever event (overall) by study vaccine group based on the number of subjects contributing any follow up safety information for at least one data value of an individual sign/symptom. Excludes subjects with missing intensity information for the whole 7 days. Mild fever: ≥ 100.4 to < 101.3º F (≥ 38.0 to < 38.5º C). Moderate fever: ≥ 101.3 to < 102.2º F (≥ 38.5 to < 39.0º C). Severe fever: ≥ 102.2º F (≥ 39.0º C). | 7 days after each administration of vaccine. | 
| The Frequency and Intensity of Solicited Local Adverse Events (AEs) Occurring During the 7 Days After Each Administration of CSL TIV or the Comparator Influenza Virus Vaccine. | The overall frequency and intensity of solicited local Adverse Events (AEs) occurring during the 7 days after each administration of bioCSL TIV or the comparator influenza virus vaccine. Percentage of subjects who experienced each event are based on the number of subjects in the Safety Population group. Excludes subjects with missing intensity information for the whole 7 days. Percentages for intensity are based on the number of subjects with non-missing intensity data. Only the maximum intensity experienced between Day 1 and Day 7 are presented for each subject. | 7 days after each administration of vaccine. | 
| The Frequency and Intensity of Solicited Systemic AEs Occurring During the 7 Days After Each Administration of CSL TIV or the Comparator Influenza Virus Vaccine. | The overall frequency and intensity of solicited systemic Adverse Events (AEs) occurring during the 7 days after each administration of CSL TIV or the comparator influenza virus vaccine. Percentage of subjects who experienced each event are based on the number of subjects in the Safety Population group. Excludes subjects with missing intensity information for the whole 7 days. Percentages for intensity are based on the number of subjects with non-missing intensity data. Only the maximum intensity experienced between Day 1 and Day 7 are presented for each subject. | 7 days after each administration of vaccine. | 
| The Frequency and Intensity of Unsolicited AEs Occurring During the 7 Days After Each Administration of CSL TIV or the Comparator Influenza Virus Vaccine. | The overall frequency and intensity of unsolicited Adverse Events (AEs) occurring during the 7 days after each administration of CSL TIV or the comparator influenza virus vaccine. Percentage of subjects who experienced each event are based on the number of subjects in the Safety Population group. Excludes subjects with missing intensity information for the whole 7 days. If a subject has multiple events of the same intensity or causality, then they are counted only once in that intensity or causality. However, subjects can be counted more than once overall. | 7 days after each administration of vaccine. | 
| The Incidence of Serious Adverse Events (SAEs) Occurring up to 7 Days After the Last Administration of CSL TIV or the Comparator Influenza Virus Vaccine. | The number of subjects experiencing at least one SAE. | 7 days after each administration of vaccine. |