Clinical Study to Evaluate Safety, Immunogenicity of Investigational Flu Vaccine Compared to an Approved Flu Vaccine (QIV) in Children Previously Vaccinated in Trial V118_05

Study Overview
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Brief Summary
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Safety, Immunogenicity of an Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine Compared to Non-Adjuvanted Comparator Influenza Vaccine in Children Previously Vaccinated in Trial V118_05

Official Title
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A Phase III, Randomized, Observer Blind, Multicenter Study to Evaluate the Safety and Immunogenicity of Repeated Exposure to an Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine (aQIV), Administered to Subjects Previously Vaccinated in Trial V118_05

Conditions
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Influenza

Intervention / Treatment
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* Biological: Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine (aQIV)
* Biological: non-adjuvanted Quadrivalent Influenza Vaccine (QIV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject who has completed their Day 181 clinic visit for non-naïve subjects or their Day 209 clinic visit for naïve subjects in parent study. Individuals who give written informed consent, who can comply with study procedures, and who are available for follow-up Exclusion Criteria: Individuals recently vaccinated against influenza. Subjects with contraindications to receive influenza vaccine. Please contact the site for additional eligibility criteria.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 84 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aQIV<br>Adjuvanted Quadrivalent Subunit Influenza | Biological: Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine (aQIV)<br>* 1 dose 0.25 ml: ≥6 months to <36 months, 0.5 ml: ≥36 months to <72 months<br>|
| Active Comparator: QIV<br>Non-Adjuvanted Quadrivalent Subunit Influenza | Biological: non-adjuvanted Quadrivalent Influenza Vaccine (QIV)<br>* 1 dose 0.25 ml: ≥6 months to <36 months, 0.5 ml: ≥36 months to <72 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoint: Number of Subjects With SAEs, AEs Leading to Withdrawal From the Study, NOCDs, AESIs and Medically Attended AEs. | Safety was assessed in terms of number of subjects between 12 months and 7 years of age reporting unsolicited events up to 12 months after last vaccination with either aQIV or QIV (comparator): serious adverse events (SAEs), AEs leading to study withdrawal, new onset chronic disease (NOCDs), adverse events of special interest (AESIs) and medically attended AEs after vaccination. | Day 1 through Day 356 | 
| Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion and Differences in Percentage of Subjects Achieving Seroconversion for Homologous Influenza Strains (Day 22) | The percentage of subjects achieving seroconversion at Day 22 after vaccination is reported for homologous strains; Seroconversion is defined as hemagglutination inhibition (HI) ≥1:40 for subjects negative at baseline [<1:10]; or a minimum 4-fold increase in HI titer for subjects positive at baseline [HI ≥1:10]; Strains tested: A/H1N1 is Influenza A H1N1 California/7/2009 Egg Ab; A/H3N2 is Influenza A H3N2 Texas/50/2012 Ab; B/Yamagata is Influenza B Massachusetts/2/2012 Ab; B/Victoria is Influenza B Brisbane/60/2008 Egg Ab | Day 1, Day 22 | 
| Immunogenicity Endpoint: Percentage of Subjects Achieving HI Titer ≥ 1:40 and and Differences in Percentage of Subjects Achieving HI Titer ≥ 1:40 for Homologous Influenza Strains (Day 22). | The percentage of subjects achieving HI titer ≥1:40 at Day 22 after vaccination is reported for homologous strains. Strains tested: A/H1N1 is Influenza A H1N1 California/7/2009 Egg Ab; A/H3N2 is Influenza A H3N2 Texas/50/2012 Ab; B/Yamagata is Influenza B Massachusetts/2/2012 Ab; B/Victoria is Influenza B Brisbane/60/2008 Egg Ab | Day 1, Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoint: Number of Subjects With a Diagnosis of Failure to Thrive or Short Stature | Short stature was defined as a height/length that was 2 or more standard deviations below the mean for age and gender within a population and was assessed as being below the 2nd z-score (worse outcome) on the length/height-for-age scale. Failure-to-thrive was defined by inadequate weight gain and physical growth and assessed through 2 or more of the following criteria: height/length-for-age, weight-for-age or weight-for-height/length below the 2nd z-score, a child's growth line crossing a z-score line, a sharp change in growth curve or a curve that remains flat. The observations were made for 2 or more time points each divided by at least 2 months. | Day 1 through Day 366 (Day 1, Day 22, Day 181, Day 366) | 
| Safety Endpoint: Number of Subjects With Any Unsolicited AEs | Safety was assessed in terms of number of subjects between 12 months and 7 years of age reporting unsolicited events up to 12 months after last vaccination with either aQIV or QIV (comparator). | Day 1 through Day 22 | 
| Safety Endpoint: Number of Subjects With Solicited Local and Systemic Adverse Events (AEs) | Safety was assessed in terms of number of subjects between 12 months and 7 years of age reporting solicited local and systemic AEs, day 1 to day 7 after vaccination with either aQIV or QIV (comparator). | Up to 7 days following vaccination | 
| Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion and Differences in Percentage of Subjects Achieving Seroconversion for Homologous Influenza Strains (Day 181) | The percentage of subjects achieving seroconversion at Day 181 after vaccination is reported for homologous strains. Seroconversion is defined as HI ≥1:40 for subjects negative at baseline [<1:10]; or a minimum 4-fold increase in HI titer for subjects positive at baseline [HI ≥1:10]; Strains tested: A/H1N1 is Influenza A H1N1 California/7/2009 Egg Ab; A/H3N2 is Influenza A H3N2 Texas/50/2012 Ab; B/Yamagata is Influenza B Massachusetts/2/2012 Ab; B/Victoria is Influenza B Brisbane/60/2008 Egg Ab. | Day 1, Day 181 | 
| Immunogenicity Endpoint: Percentage of Subjects Achieving HI Titer ≥ 1:40 and Difference in Percentage of Subjects Achieving HI Titer ≥ 1:40 for Homologous Influenza Strains (Day 181) | The percentage of subjects achieving HI titer ≥1:40 at Day 181 after vaccination is reported for homologous strains; Strains tested: A/H1N1 is Influenza A H1N1 California/7/2009 Egg Ab; A/H3N2 is Influenza A H3N2 Texas/50/2012 Ab; B/Yamagata is Influenza B Massachusetts/2/2012 Ab; B/Victoria is Influenza B Brisbane/60/2008 Egg Ab | Day 1, Day 181 | 
| Immunogenicity Endpoint: Geometric Mean HI Titers (GMTs) and GMT Ratios for Homologous Influenza Strains (Day 1, Day 22, Day 181) | Adjusted GMT, GMR and 95% confidence interval (CI) were analyzed using ANCOVA with study specific covariates. Strains tested: A/H1N1 is Influenza A H1N1 California/7/2009 Egg Ab; A/H3N2 is Influenza A H3N2 Texas/50/2012 Ab; B/Yamagata is Influenza B Massachusetts/2/2012 Ab; B/Victoria is Influenza B Brisbane/60/2008 Egg Ab | Day 1, Day 22, Day 181 | 
| Immunogenicity Endpoint: Geometric Mean Ratios (GMR) for Homologous Influenza Strains | The GMR is the geometric mean of the fold increase in HI titer from Day 1 to Day 22 or Day 181. Adjusted GMT, GMR and 95% CI were analyzed using ANCOVA with study specific covariates. Strains tested: A/H1N1 is Influenza A H1N1 California/7/2009 Egg Ab; A/H3N2 is Influenza A H3N2 Texas/50/2012 Ab; B/Yamagata is Influenza B Massachusetts/2/2012 Ab; B/Victoria is Influenza B Brisbane/60/2008 Egg Ab | Day 1, Day 22, and Day 181 | 
| Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion and Difference in Percentage of Subjects Achieving Seroconversion for Heterologous Influenza Strains (Day 181) | The percentage of subjects achieving seroconversion at Day 181 after vaccination is reported for homologous strains. Seroconversion is defined as HI ≥1:40 for subjects negative at baseline [<1:10]; or a minimum 4-fold increase in HI titer for subjects positive at baseline [HI ≥1:10]; Strains tested: A/H3N2 is Influenza A H3N2 Hong Kong/2014 Ab; B/Yamagata is Influenza B Phuket/2013 Ab | Day 1, Day 181 | 
| Immunogenicity Endpoint: Percentage of Subjects Achieving HI Titer ≥ 1:40 and Difference in Percentage of Subjects Achieving HI Titer ≥ 1:40 for Heterologous Influenza Strains (Day 181) | The percentage of subjects achieving HI titer ≥1:40 at Day 181 after vaccination is reported for homologous strains; Strains tested: A/H3N2 is Influenza A H3N2 Hong Kong/2014 Ab; B/Yamagata is Influenza B Phuket/2013 Ab | Day 1, Day 181 | 
| Immunogenicity Endpoint: Geometric Mean HI Titers (GMTs) for Heterologous Influenza Strains (Day 1, Day 22, Day 181) | Adjusted GMT, GMR and 95% CI were analyzed using ANCOVA with study specific covariates. Strains tested: A/H3N2 is Influenza A H3N2 Hong Kong/2014 Ab; B/Yamagata is Influenza B Phuket/2013 Ab | Day 1, Day 22, Day 181 | 
| Immunogenicity Endpoint: Geometric Mean Ratios (GMR) for Heterologous Influenza Strains | The GMR is the geometric mean of the fold increase in HI titer from Day 1 to Day 22 or Day 181. Adjusted GMT, GMR and 95% CI were analyzed using ANCOVA with study specific covariates. Strains tested: A/H3N2 is Influenza A H3N2 Hong Kong/2014 Ab; B/Yamagata is Influenza B Phuket/2013 Ab | Day 1, Day 22, and Day 181 |