Clinical Study to Evaluate Safety, Immunogenicity of Investigational Flu Vaccine Compared to an Approved Flu Vaccine in Children Previously Vaccinated in Trial V118_05 (NCT01964989)

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. Subjects will receive either the Same or Alternate Type of Vaccine.

Official Title
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A Phase III, Randomized, Observer Blind, Multicenter Study to Evaluate the Safety and Immunogenicity of Repeated Exposure to Either the Same or Alternate Type of Vaccine, Adjuvanted or Non-adjuvanted Quadrivalent Subunit Influenza Virus Vaccine (aQIV or QIV), Administered to Subjects Previously Vaccinated in Trial V118_05 (NCT01964989)

Conditions
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Influenza

Intervention / Treatment
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* Biological: Adjuvanted QIV (aQIV)
* Biological: Non-adjuvanted QIV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to participate in this study, all subjects must meet ALL of the inclusion criteria described. Subject's parent/legal guardian has voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. Male or female subject who has completed their Visit 13 (Study Day 366 for non-naïve subjects) or clinic Visit 15 (Day 390 for naïve subjects) in parent trial V118_05. For naïve subjects in parent trial V118_05 to have received two doses of the same study vaccine (i.e. 2 doses of aQIV or 2 doses of QIV). Exclusion Criteria: Previous immunization with any influenza vaccine (licensed or investigational) within 6 months prior to enrollment. Subjects with a clinical condition representing a contraindication to intramuscular vaccination or blood draws. Unwillingness of the parent(s)/ legal guardian(s) of the subject to refuse to participate in another clinical trial while enrolled in V118-05E3. Additional eligibility criteria may be discussed by contacting the site.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 7 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aQIV/aQIV<br>Subjects previously vaccinated with aQIV followed one year later by aQIV | Biological: Adjuvanted QIV (aQIV)<br>* Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine (aQIV)<br>|
| Experimental: aQIV/QIV<br>Subjects previously vaccinated with aQIV followed one year later by QIV | Biological: Non-adjuvanted QIV<br>* Non-adjuvanted Quadrivalent Influenza Vaccine (QIV)<br>|
| Experimental: QIV/aQIV<br>Subjects previously vaccinated with QIV followed one year later by aQIV | Biological: Adjuvanted QIV (aQIV)<br>* Adjuvanted Quadrivalent Subunit Influenza Virus Vaccine (aQIV)<br>|
| Experimental: QIV/QIV<br>Subjects previously vaccinated with QIV followed one year later by QIV | Biological: Non-adjuvanted QIV<br>* Non-adjuvanted Quadrivalent Influenza Vaccine (QIV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio as Determined by Hemagglutination Inhibition (HI) Assay on Day 22 Against Homologous Strains (aQIV-primed Comparison), Noninferiority Analysis | GMT and 95% confidence interval (CI) were analyzed for Day 22 against homologous strains using ANCOVA with study specific covariates. Strains tested: A/H1N1 California/07/2009; A/H3N2 Switzerland/9715293/2013; B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 22 | 
| Immunogenicity Endpoint: GMT and GMT Ratio as Determined by HI Assay on Day 22 Against Homologous Strains (aQIV-primed Comparison), Superiority Analysis | GMT and 95% CI were analyzed for Day 22 against homologous strains using ANCOVA with study specific covariates. Strains tested: A/H1N1 California/07/2009; A/H3N2 Switzerland/9715293/2013; B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity Endpoint: GMT and GMT Ratio as Determined by HI Assay on Day 22 Against Homologous Strains (QIV-primed Comparison) | GMT and 95% CI were analyzed for Day 22 against homologous strains using ANCOVA with study specific covariates. Strains tested: A/H1N1 California/07/2009; A/H3N2 Switzerland/9715293/2013; B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 22 | 
| Immunogenicity Endpoint: GMT and GMT Ratio as Determined by HI Assay on Day 181 Against Homologous Strains (aQIV-primed and QIV-primed Comparison) | GMT and 95% CI were analyzed for Day 181 against homologous strains using ANCOVA with study specific covariates. Strains tested: A/H1N1 California/07/2009; A/H3N2 Switzerland/9715293/2013; B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 181 | 
| Immunogenicity Endpoint: Seroconversion Rate (SCR) on Day 22 Against Homologous Strains (aQIV-primed and QIV-primed Comparison) | The percentage of subjects achieving seroconversion at Day 22 after vaccination is reported against homologous strains. Seroconversion was defined in subjects seronegative at baseline (i.e. HI titer <1:10 on Day 1) as postvaccination HI titer ≥1:40 and defined in subjects seropositive at baseline (i.e. HI titer ≥1:10 on Day 1) as a minimum of a 4-fold increase in post-vaccination HI titer. Strains tested: A/H1N1 California/07/2009; A/H3N2 Switzerland/9715293/2013; B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 1, Day 22 | 
| Immunogenicity Endpoint: Geometric Mean Ratio (GMR) as Determined by HI Assay for Day 22/Day 1 and Day 181/Day 1 for Against Homologous Strains | The GMR is the geometric mean of the fold increase in HI titer from Day 1 to Day 22 or Day 181. GMR and 95% CI were analyzed against homologous strains using ANCOVA with study specific covariates. Strains tested: A/H1N1 California/07/2009; A/H3N2 Switzerland/9715293/2013; B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 22, Day 181 | 
| Immunogenicity Endpoint: Percentage of Subjects With HI Titer ≥1:40 on Day 22 and Day 181 Against Homologous Strains | The percentage of subjects achieving HI titer ≥1:40 at Day 22 and Day 181 after vaccination is reported against homologous strains. Strains tested: A/H1N1 California/07/2009; A/H3N2 Switzerland/9715293/2013; B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 22, Day 181 | 
| Immunogenicity Endpoints: Percentage of Subjects With HI Titer ≥1:110, ≥1:151, ≥1:215, ≥1:330 and ≥1:629 on Day 22 Against Homologous Strains | The percentage of subjects achieving HI Titers ≥1:110, ≥1:151, ≥1:215, ≥1:330 and ≥1:629 at Day 22 after vaccination is reported against homologous strains. Strains tested: A/H1N1 California/07/2009; A/H3N2 Switzerland/9715293/2013; B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 22 | 
| Immunogenicity Endpoint: GMT as Determined by HI Assay on Day 1, Day 22, and Day 181 Against Heterologous Strains | GMT and 95% CI were analyzed for Day 22 for the heterologous strains using ANCOVA with study specific covariates. The two heterologous strains selected for HI testing in this study were the H3N2 strain, A/Hong Kong/4801/2014 (X-263B), and the B/ Victoria lineage strain, B/Malaysia/2506/2004. | Day 1, Day 22, Day 181 | 
| Immunogenicity Endpoint: GMR as Determined by HI Assay for Day 22/Day 1 and Day 181/Day 1 Against Heterologous Strains | The GMR is the geometric mean of the fold increase in HI titer from Day 1 to Day 22 or Day 181. GMR and 95% CI were analyzed for the heterologous strains using ANCOVA with study specific covariates. The two heterologous strains selected for HI testing in this study were the H3N2 strain, A/Hong Kong/4801/2014 (X-263B), and the B Victoria lineage strain, B/Malaysia/2506/2004. | Day 22/Day 1 and Day 181/Day 1 | 
| Immunogenicity Endpoint: Percentage of Subjects Achieving SCR and HI Titer ≥1:40 on Day 22 and Day 181 Against Heterologous Strains | The percentage of subjects achieving HI titer ≥1:40 at Day 22 and Day 181 after vaccination and the percentage of subject who experienced seroconversion is reported for homologous strains. Seroconversion was defined in subjects seronegative at baseline (i.e. HI titer <1:10 on Day 1) as post-vaccination HI titer ≥1:40 and defined in subjects seropositive at baseline (i.e. HI titer ≥1:10 on Day 1) as a minimum of a 4-fold increase in post-vaccination HI titer. The two heterologous strains selected for HI testing in this study were the H3N2 strain, A/Hong Kong/4801/2014 (X-263B), and the B/Victoria lineage strain, B/Malaysia/2506/2004. | Day 22, Day 181 | 
| Immunogenicity Endpoint: GMT as Determined by Microneutralization (MN) Assay on Day 1, Day 22, and Day 181 Against Homologous Strains | To further characterize immune response, MN GMT and 95% CI were analyzed for Day 1, Day 22, and Day 181 against homologous strains. Strains tested: A/H1N1 California/07/2009; A/H3N2 Switzerland/9715293/2013; B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 1, Day 22, Day 181 | 
| Immunogenicity Endpoint: GMR as Determined by MN Assay for Day 22/Day 1 and Day 181/Day 1 Against Homologous Strains | The GMR is the geometric mean of the fold increase in MN titer from Day 1 to Day 22 or Day 181. GMR and 95% CI were analyzed for the homologous strains using ANCOVA with study specific covariates. Strains tested: A/H1N1 California/07/2009; A/H3N2 Switzerland/9715293/2013; B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 22/Day 1 and Day 181/Day 1 | 
| Immunogenicity Endpoint: Anti-neuraminidase (NA) GMTs on Day 1, Day 22, and Day 181 Against Homologous Strains | To further characterize immune response, adjusted anti-NA GMT and 95% CI were analyzed for Day 1, Day 22, and Day 181 against homologous strains. Strains tested: N1 (PR8 H6N1 California/07/2009), N2 (PR8 H6N2 Switzerl/9715293/2013); B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 1, Day 22, Day 181 | 
| Immunogenicity Endpoint: Anti-NA GMR for Day 22/Day 1 and Day 181/Day 1 Against Homologous Strains | The GMR is the geometric mean of the fold increase in anti-NA titer from Day 1 to Day 22 or Day 181. GMR and 95% CI were analyzed against homologous strains using ANCOVA with study specific covariates. Strains tested: N1 (PR8 H6N1 California/07/2009), N2 (PR8 H6N2 Switzerl/9715293/2013); B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 22/Day 1 and Day 181/Day 1 | 
| Safety Endpoint: Percentage of Subjects With Solicited AEs | Safety of revaccination was assessed in terms of percentage of subjects reporting solicited AEs up to 7 days after vaccination. | Day 1 to Day 7 after vaccination | 
| Safety Endpoint: Percentage of Subjects With Unsolicited AEs | Safety of revaccination was assessed in terms of percentage of subjects reporting unsolicited AEs during the overall study period (Day 1 to Day 366). | Day 1 to Day 366 | 
| Safety Endpoint: Percentage of Subjects With Serious Adverse Events (SAE), AEs Leading to Withdrawal, New Onset of Chronic Disease (NOCD), AE of Special Interest (AESI), and Medically Attended AE. | Safety of revaccination was assessed in terms of percentage of subjects reporting SAEs, AEs leading to withdrawal, NOCD, AESI and medically attended AE. Each subject was followed for a period of 12 months after receipt of the study vaccine. NOCDs include AEs that represents a new diagnosis of a chronic medical condition that was not present or suspected in a subject prior to study enrollment. AESIs include potentially immune-mediated disorders which were reported by the investigators. | Day 1 to Day 366 | 
| Safety Endpoint: Percentage of Subjects With Diagnosis of Failure to Thrive or Short Stature | Safety of revaccination was assessed in terms of percentage of subjects reporting diagnosis of failure to thrive or short stature up to 12 months after last vaccination. | Day 1 to Day 366 | 
| Safety Endpoint: Percentage of Subjects With Otitis Media, or Pneumonia, or Influenza-like Illness | Safety of revaccination was assessed in terms of percentage of subjects reporting otitis media, or pneumonia, or influenza-like illness up to 12 months after last vaccination. | Day 1 to Day 366 | 
| Immunogenicity Endpoint: Percentage of Subjects With MN Titer ≥1:20, ≥1:40, ≥1:80, ≥1:160, ≥1:320 and ≥1:640 on Day 22 and Day 181 Against Homologous Strains | The percentage of subjects achieving MN titer ≥1:20, ≥1:40, ≥1:80 ≥1:160, ≥1:320 and ≥1:640 at Day 22 and Day 181 after vaccination is reported against homologous strains. Strains tested: A/H1N1 California/07/2009; A/H3N2 Switzerland/9715293/2013; B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 22, Day 181 | 
| Immunogenicity Endpoint: Percentage of Subjects Achieving Anti-NA Titers ≥1:20, ≥1:40, ≥1:80, ≥1:160, ≥1:320 and ≥1:640 on Days 22 and 181 Against Homologous Strains | The percentage of subjects achieving anti-NA titers ≥1:20, ≥1:40, ≥1:80, ≥1:160, ≥1:320 and ≥1:640 on Days 22 and 181 after vaccination is reported against homologous strains Strains tested: N1 (PR8 H6N1 California/07/2009), N2 (PR8 H6N2 Switzerl/9715293/2013); B/Victoria Brisbane/60/2008; B/Yamagata Phuket/3073/2013. | Day 22, Day 181 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza Vaccine, MF59 adjuvant