Safety, Reactogenicity and Immunogenicity of Flublok Quadrivalent (Recombinant Influenza Vaccine,Seasonal Formulation)

Study Overview
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Brief Summary
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Flublok was studied previously in children 6 -59 months of age and demonstrated less than satisfactory immunogenicity results, especially in the 6-36 month age group. Thus, the initial introduction of Flublok Quadrivalent Formulation (RIV4) into the pediatric population will evaluate immunogenicity and safety older children and adolescents, aged 6-17. This clinical trial is designed to demonstrate safety and non-inferior immunogenicity of Flublok-Q in pediatric subjects 6-17 years of age as compared to IIV4. Positive results in this study may support further studies in younger children.

Detailed Description
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The U.S. Advisory Committee on Immunization Practices (ACIP) recommends that all people ≥6 months of age receive influenza vaccine annually. Recommendations for influenza immunization of children vary somewhat among countries in the European Union, but immunization of children at high risk for complications of influenza infection is recommended by WHO and according to criteria in most countries. Currently, the immunization practices are progressing to quadrivalent formulations of inactivated influenza vaccines (IIV4) which are approved in the US for most of the indicated population. Additionally, live attenuated vaccine (LAIV4) is approved in the U.S. for individuals aged 2-49 years and Flublok®(RIV3), a purified trivalent recombinant hemagglutinin protein vaccine is approved in the U.S. for adults 18-49 years of age. Children are at particular risk of complications of influenza, including the B lineages, so expansion of the Flublok indication into the pediatric age group with a quadrivalent formulation is warranted.

Official Title
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Evaluation of the Safety, Reactogenicity and Immunogenicity of Flublok Quadrivalent (Quadrivalent Recombinant Influenza Vaccine,Seasonal Formulation) Administered Intramuscularly to Healthy Children and Adolescents Age 6-17 Years

Conditions
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Influenza

Intervention / Treatment
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* Biological: Flublok® Quadrivalent Influenza Virus Vaccine
* Biological: Fluarix Quadrivalent® Influenza Virus Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age 6-17 years (Cohort A: 6-8 years of age; Cohort B: 9-17 years of age) Female subjects of child-bearing potential (as defined by the onset of menses) must agree to avoid becoming pregnant and to use effective method of contraception or practice abstinence for at least 28 day prior to the first study vaccine administration, until the completion of the study. Female subjects of child-bearing potential must have a negative pregnancy test within 24 hours prior to vaccine administration. In good general health, as determined by medical history and targeted physical examination, if indicated The parent(s) or legal representative(s) of each potential subject must: Comprehend the study requirements and agree to comply with planned study procedures and visits Provide written consent prior to enrollment and initiation of any study procedures Pediatric assent will be obtained in accordance with the Institutional Review Board/Independent Ethics Committee determination. Exclusion Criteria: Known allergy to eggs, severe allergy (e.g. anaphylaxis) to other components of either vaccine or contraindications to receipt of the comparator IIV4 Immunosuppression as a result of an underlying illness or treatment. Note: Subjects on nasal or topical steroids will be allowed Active neoplastic disease or a history of any malignancy. History of receiving influenza vaccine within the past 6 months or plans during the study to receive influenza vaccine outside of this study. History of receiving immunoglobulin or other blood product within the 3 months prior to enrollment in this study. Receipt of any non-study licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study, or plans during the study to receive a licensed vaccine within 4 weeks of a study dose [See above for influenza vaccines]. Acute or chronic medical condition that, in the opinion of the investigator, would render immunization unsafe or would interfere with the evaluation of immune responses History of severe reactions following immunization. An acute illness, including a body temperature greater than 100*F, within 3 days prior to immunization. Receipt of an experimental vaccine or medication within 1 month prior to enrollment in this study, or expectation of receiving an experimental vaccine, medication, or blood product during the study Stage in which the subject will participate. Developmental delay, neurologic disorder, or seizure disorder requiring ongoing medical management (note: history of seizure is not an exclusion criterion). Any other condition or situation that would, in the opinion of the investigator, place the potential subject an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol. History of Guillain-Barré syndrome. Known pregnancy, positive urine or serum pregnancy test within 24 hours prior to planned study vaccination, or breast-feeding. Concurrent participation in another clinical trial (in active or follow-up phase).

Ages Eligible for Study
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Minimum Age: 6 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group 1, Flublok<br>Participants at 9 years to 17 years of age at enrollment, Flublok® Quadrivalent Influenza Virus Vaccine | Biological: Flublok® Quadrivalent Influenza Virus Vaccine<br>* Intramuscular (Relevant year formulation)<br>* Other names: Recombinant Hemagglutinin;|
| Active Comparator: Study Group 2, Fluarix<br>Participants at 9 years to 17 years of age at enrollment, Fluarix Quadrivalent® Influenza Virus Vaccine | Biological: Fluarix Quadrivalent® Influenza Virus Vaccine<br>* Intramuscular (Relevant year formulation)<br>|
| Experimental: Study Group 3, Flublok<br>Participants at 6 years to 8 years of age at enrollment, Flublok® Quadrivalent Influenza Virus Vaccine | Biological: Flublok® Quadrivalent Influenza Virus Vaccine<br>* Intramuscular (Relevant year formulation)<br>* Other names: Recombinant Hemagglutinin;|
| Active Comparator: Study Group 4, Fluarix<br>Participants at 6 years to 8 years of age at enrollment, Fluarix Quadrivalent® Influenza Virus Vaccine | Biological: Fluarix Quadrivalent® Influenza Virus Vaccine<br>* Intramuscular (Relevant year formulation)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Solicited Injection Site and Systemic Events and Unsolicited Adverse Events Following Vaccination With Quadrivalent Vaccine. | Solicited injection site reactions: Pain, Bruising, Redness, and Swelling; Solicited systemic reactions: Headache, Chills, Fever, Fatigue, Muscle Pain, Joint Pain and Nausea. | Day 0 up to Day 28 post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers of Antibodies to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Immunogenicity will be evaluated prior to vaccination and at 28 days after vaccination using the hemagglutination inhibition (HAI) technique. For each influenza vaccine strain, pre and post vaccination geometric mean titers (GMTs) and seroprotection and seroconversion will be calculated. | Day 0 and Day 28 after final vaccination (Cohort B includes 1-Dose subjects at Day 28 and 2-Dose subjects at Day 56) | 
| Seroconversion to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Seroconversion is defined as: Either a pre vaccination titer < 10 (1/dil) and a post vaccination titer ≥ 40 (1/dil), or a pre vaccination titer ≥ 10 (1/dil) and a ≥ 4 fold increase in post vaccination titer at Day 28 after the final vaccination. | Day 28 after final vaccination | 
| Seroprotection to Vaccine Antigens Following Vaccination With Quadrivalent Vaccine | Seroprotection is defined as: A titer ≥ 40 (l/dil) at pre vaccination and at Day 28 after the final vaccination. | Day 28 after final vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention