Safety and Immunogenicity of an Adjuvanted Trivalent Influenza Vaccine in Children 6 to <72 Months of Age in Mexico.

Study Overview
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Brief Summary
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The administration of adjuvanted Trivalent Influenza Vaccine (aTIV) has come to result in a more immunogenic and effective response compared with conventional influenza vaccines in elderly and adults. The aim of this study is to evaluate safety and immunogenicity of Novartis aTIV in children 6 to <72 months of age, Mexican population, in comparison to Fluzone, a non-adjuvanted trivalent influenza vaccine (TIV).

Official Title
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A Phase 3, Observed-Blind, Randomized, Multi-center Study to Evaluate Safety and Immunogenicity of an Adjuvanted Trivalent Influenza Vaccine in Children 6 to <72 Months of Age in Mexico.

Conditions
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Influenza

Intervention / Treatment
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* Biological: Adjuvanted Trivalent Influenza Vaccine, 1 dose for non-naive subjects (day 1), two doses for naive subjects (day 1 and day 29)
* Biological: Non-adjuvanted Trivalent Influenza Vaccine, 1 dose for non-naive subjects (day 1), two doses for naive subjects (day 1 and day 29).


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals of >6 months through <72 months of age on the day of informed consent. Individuals whose parent(s)/legal guardian(s) have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. Individuals who can comply with study procedures. Willingness to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterize immune response. Exclusion Criteria: Progressive, unstable or uncontrolled clinical conditions. Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study. History of progressive or severe neurologic disorder, seizure disorder or Guillain-Barré syndrome. Surgery planned during the study period that in the Investigator's opinion would interfere with the study visits schedule. Known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. Any fatal prognosis of an underlying medical condition (<12 month life expectancy). Clinical conditions representing a contraindication to intramuscular vaccination and blood draws. Abnormal function of the immune system resulting from: Clinical conditions. Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to informed consent. Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent. Received immunoglobulins or any blood products within 180 days prior to informed consent. Received an investigational or non-registered medicinal product within 30 days prior to informed consent. Study personnel as an immediate family or household member. Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study. Received any influenza vaccine (licensed or investigational) or with laboratory confirmed influenza within 6 months prior enrollment. Received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrolment in this study or who are planning to receive any vaccine within 28 days from the study vaccines.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 71 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aTIV<br>aTIV is a trivalent influenza virus vaccine, adjuvanted with MF59C. | Biological: Adjuvanted Trivalent Influenza Vaccine, 1 dose for non-naive subjects (day 1), two doses for naive subjects (day 1 and day 29)<br>* A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV, a trivalent (surface antigen, formaldehyde-inactivated) influenza virus vaccine, adjuvanted with MF59C.1, administered at day 1 (for all subjects) and day 29 (for naïve subjects).<br>|
| Active Comparator: TIV<br>TIV is trivalent influenza vaccine licensed in Mexico. | Biological: Non-adjuvanted Trivalent Influenza Vaccine, 1 dose for non-naive subjects (day 1), two doses for naive subjects (day 1 and day 29).<br>* A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV , an egg-derived trivalent split influenza vaccine licensed in Mexico, administered at day 1 (for all subjects) and day 29 (for naïve subjects)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Naive Subjects 6 to < 36 Months Old Reporting Solicited Local and Systemic Adverse Events (AEs) From Day 1 to Day 7 Following Each Vaccination. | Number of naive subjects 6 to < 36 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after first vaccination and from Day 29 to Day 35 after second vaccination. | From Day 1 to Day 7 by vaccination | 
| Number of Non-naive Subjects 6 to < 36 Months Old Reporting Solicited Local and Systemic AEs From Day 1 to Day 7 After Vaccination. | Number of non-naive subjects 6 to < 36 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after vaccination. | From Day 1 to Day 7 | 
| Number of Naive Subjects ≥ 36 Months to < 72 Months Old Reporting Solicited Local and Systemic AEs From Day 1 to Day 7 Following Each Vaccination. | Number of naive subjects ≥ 36 months to < 72 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after first vaccination and from Day 29 to Day 35 after second vaccination. | From Day 1 to Day 7 by vaccination | 
| Number of Non-naive Subjects ≥36 Months to < 72 Months Old Reporting Solicited Local and Systemic AEs From Day 1 to Day 7 Following Each Vaccination. | Number of non-naive subjects ≥36 months to < 72 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after vaccination. | From Day 1 to Day 7 | 
| Number of Naive Subjects Aged 6 to < 72 Months Reporting All Unsolicited AEs From Day 1 to Day 50. | Number of naive subjects aged 6 to < 72 months reporting all unsolicited AEs, medically attended AEs, AE leading to study withdrawal and serious AEs (SAEs) from Day 1 to Day 50. | From Day 1 to Day 50 | 
| Number of Non-naive Subjects Aged 6 to < 72 Months Reporting All Unsolicited AEs From Day 1 to Day 22 | Number of non-naive subjects aged 6 to < 72 months reporting all unsolicited AEs, medically attended AEs, AE leading to study withdrawal and SAEs from Day 1 to Day 22. | From Day 1 to Day 22 | 
| Geometric Mean Titers (GMTs), in All Three Homologous Virus Strains in Subjects 6 to < 72 Months of Age. | Antibody response was assessed in terms of GMTs in all three homologous virus strains, 21 days after last immunization, in subjects 6 to <72 months of age. The study is considered a success if the 21 days after last immunization GMT ratios of aTIV relative to TIV demonstrate as non-inferior with the lower limit (LL) of the two sided 95% confidence interval (CI) above 0.67 (-0.176 on log10 scale) for each vaccine strain (Center for Biologics Evaluation and Research {CBER} Guideline on Seasonal Vaccines May 2007). | Day 1 and Day 22 (vaccine non-naïve subjects) or Day 50 (vaccine naïve subjects) post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects Achieving Seroconversion in Hemagglutination Inhibition (HI) Titers and Vaccine Group Differences at Day 1 and 21 Days After Last Vaccination With aTIV or TIV in Naive and Non-naive Subjects. | Percentages of subjects with seroconversion in all three homologous virus strains, 21 days after last immunization, in subjects 6 to <72 months of age, defined as: HI ≥ 40 subject with a pre-vaccination HI titer <10; a minimum 4-fold increase HI titer for subjects with a prevaccination HI titer ≥10, on Day 22 (non-naive subjects) or Day 50 (naive subjects), as applicable. | Day 1 and Day 22 (vaccine non-naive subjects) or Day 50 (vaccine naive subjects) post vaccination | 
| Geometric Mean Ratios (GMRs) of HI and Vaccine Group Differences at Day 1 and 21 Days After Last Vaccination With aTIV or TIV in Naive and Non-naive Subjects. | GMRs of HI, day 22/day 1 (non-naive subjects) or day 50/day 1 (naive subjects) in all three homologous virus strains, 21 days after last immunization, in subjects 6 to <72 months of age. As the non-inferiority of aTIV to TIV has been established, GMT ratio of aTIV relative to TIV in all three homologous virus strains, 21 days after last immunization in subjects 6 to <72 months of age was evaluated using margins greater than the non-inferiority cut-off of 0.67. | Day 1 and Day 22 (vaccine non-naive subjects) or Day 50 (vaccine naive subjects) post vaccination | 
| Percentages of Subjects With a HI Titer ≥ 40, ≥110 and ≥330 and Vaccine Group Differences at Day 1 and 21 Days After Last Vaccination With aTIV or TIV in Naive and Non-naive Subjects. | Percentage of subjects with a HI titer ≥ 40, ≥110 and ≥330 on Day 1, Day 22 (non naïve subjects) or Day 50 (naïve subjects), in all three homologous virus strains, 21 days after last immunization, in subjects 6 to <72 months of age. | Day 1 and Day 22 (vaccine non-naive subjects) or Day 50 (vaccine naive subjects) post vaccination |