CT18 Infant Influenza Priming Study in Vaccine Naive Infants

Study Overview
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Brief Summary
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This study evaluates whether priming influenza naive infants, age six to 23 months, with a MF59-adjuvanted (oil in water emulsion) influenza vaccine is preferred to priming with an inactivated unadjuvanted influenza vaccine. All participants will receive a priming vaccine, either MF59-adjuvanted trivalent influenza vaccine (aTIV) or unadjuvanted quadrivalent influenza vaccine (QIV). For the booster shot the following year, two thirds of participants will receive QIV and one third will receive MF59-adjuvanted vaccine.

Detailed Description
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Children under 24 months of age suffer from an influenza burden (high morbidity and mortality) similar to that of the elderly, and have been identified as a high priority target for vaccination programs by Canada's National Advisory Committee on Immunization. There is evidence that a person's first exposure to influenza antigens may have long-term implications for protection. This is a randomized, controlled, observer-blind study that will assign participants to one of three groups. Group 1 will receive MF59-adjuvanted influenza vaccine (two doses one month apart) in the fall of year 1, followed by QIV (one dose) in the fall of year 2. Group 2 will receive QIV (two doses one month apart) in the fall of year 1, followed by QIV (one dose) in the fall of year 2. Group 3 will receive MF59-adjuvanted IV (two doses one month apart) in the fall of year 1, followed by MF59-adjuvanted IV (one dose) in the fall of year 2.

Official Title
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A Randomized Controlled Observer Blind Trial to Compare the Immunogenicity and Acceptability of a MF59-adjuvanted Influenza Vaccine Compared to an Inactivated Influenza Vaccine as a Preferred Influenza Vaccine Priming Strategy for Naive Infants 6 to <24 Months of Age

Conditions
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Influenza

Intervention / Treatment
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* Biological: aTIV Primer
* Biological: QIV Primer
* Biological: aTIV Booster
* Biological: QIV Booster


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parent/LAR is willing and able to give informed consent for participation in the trial. Male or Female, aged six months to 23 months. In the Investigator's opinion, is able and willing to comply with all trial requirements. Exclusion Criteria: Any significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial. Participant in another research trial involving an investigational product or medical device in the prior 12 weeks. Prior receipt of an influenza vaccine History of laboratory-confirmed influenza infection, by parent/LAR report Hypersensitivity to any vaccine component of products used in this study (see product monographs) Immunodeficiency or autoimmune disease

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 23 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
Interventional Model Description: Participants will be randomly assigned to one of three groups: Group 1 will receive aTIV as a primer and QIV as a booster, Group 2 will receive QIV as both primer and booster, and Group 3 will receive aTIV as both primer and booster.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1: aTIV primer, QIV booster<br>Two doses (0.25 mL) aTIV (FLUAD )received one month apart in year 1. One dose (0.5 mL) QIV (Fluzone) received as booster in year 2. | Biological: aTIV Primer<br>* MF59-adjuvanted trivalent influenza virus primer: 2 doses (0.25mL) one month apart<br>* Other names: FLUAD Pediatric®;Biological: QIV Booster<br>* Unadjuvanted quadrivalent influenza vaccine booster: 1 dose (0.5mL), year 2<br>* Other names: Fluzone® Quadrivalent;|
| Other: Group 2: QIV primer, QIV booster<br>Standard of care control group: Two doses (0.5 mL) QIV (Fluzone) received one month apart in year 1. One dose (0.5 mL) QIV (Fluzone) received as booster in year 2. | Biological: QIV Primer<br>* Unadjuvanted quadrivalent influenza vaccine primer: 2 doses (0.5mL) one month apart<br>* Other names: Fluzone® Quadrivalent;Biological: QIV Booster<br>* Unadjuvanted quadrivalent influenza vaccine booster: 1 dose (0.5mL), year 2<br>* Other names: Fluzone® Quadrivalent;|
| Experimental: Group 3: aTIV primer, aTIV booster<br>This arm is experimental in that some participants will be receiving the MF59-adjuvanted TIV (FLUAD) in year two of the study, after the age of two years, which is off label. Two doses (0.25 mL) TIV (FLUAD) received one month apart in year 1. One dose (0.25 mL) TIV (FLUAD) received as booster in year 2. | Biological: aTIV Primer<br>* MF59-adjuvanted trivalent influenza virus primer: 2 doses (0.25mL) one month apart<br>* Other names: FLUAD Pediatric®;Biological: aTIV Booster<br>* MF59-adjuvanted influenza virus vaccine booster: 1 dose (0.25mL), year 2<br>* Other names: FLUAD Pediatric®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum hemagglutination inhibition (HI) antibody titers | Serum HI antibodies to influenza antigens A/H3N2, A/H1N1, and B Yamagata and Victoria lineages will be used to calculate the seroconversion rate and the seroprotection rates. | Before and after priming with the various vaccine combinations at day 393. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) | Measure local and systemic solicited and unsolicited adverse events following each vaccine dose, and severe AE throughout the study. | Days 0 to 545 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infants, priming, Fluad, Fluzone