Second Extension Study to Evaluate Safety and Tolerability of Influenza Vaccines in Adults and Elderly, and to Evaluate Immunogenicity and Concomitant Vaccination With Pneumococcal Vaccine in a Subgroup

Study Overview
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Brief Summary
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The study primarily aims to evaluate immunogenicity and safety of influenza vaccines (cell culture derived seasonal trivalent influenza vaccine (cTIV) or influenza virus vaccine (egg-derived seasonal trivalent, thiomersal free; eTIV_a)) when administered alone and when administered concomitantly with pneumococcal polysaccharide vaccine (PV) in elderly subjects. The study also aimed to evaluate safety and immunogenicity (subset) of annual vaccination with either cTIV or eTIV_a in adults and elderly subjects.

Official Title
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A Phase III, Single-Blind, Multi-Center, Extension Study to Evaluate Safety and Tolerability of a Trivalent Subunit Influenza Vaccine Produced Either in Mammalian Cell Culture or in Embryonated Hen Eggs in Adult and Elderly Subjects Who Participated in Study V58P4, With Subset Analyses of Immunogenicity and Evaluation of Concomitant Polysaccharide Pneumococcal Vaccine (Elderly).

Conditions
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Influenza

Intervention / Treatment
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* Biological: Cell culture derived seasonal trivalent influenza vaccine (cTIV)
* Biological: Influenza virus vaccine (egg-derived seasonal trivalent, thiomersal free; eTIV_a).
* Biological: cTIV or eTIV_a
* Biological: cTIV+PV OR eTIV_a+PV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: participation in the V58P4 study mentally competent to understand the nature, the scope and the consequences of the study able and willing to give written informed consent prior to study entry available for all the visits scheduled in the study Exclusion Criteria: receipt of another investigational agent within 90 days prior to, or before completion of the safety follow-up period in another study, whichever is longer, prior to Visit 7 and unwilling to refuse participation in another clinical study through the end of the present study history of any anaphylaxis, serious vaccine reactions, or allergy to any of the vaccine components any acute respiratory disease or infections requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis was acceptable) or experienced fever (i.e., axillary temperature ≥ 38°C) within the 5 days prior to Visit 7 pregnant/breast feeding women, or women of childbearing potential who refuse to use a reliable contraceptive method during the three weeks after vaccination

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cTIV<br>Cell culture derived seasonal trivalent influenza vaccine (cTIV) | Biological: Cell culture derived seasonal trivalent influenza vaccine (cTIV)<br>* cell cultured trivalent influenza vaccine (cTIV) vaccine administered as 0.5 mL single dose in the deltoid muscle, preferably of the non-dominant arm.<br>|
| Active Comparator: eTIV_a<br>Influenza virus vaccine (egg-derived seasonal trivalent, thiomersal free; eTIV_a) | Biological: Influenza virus vaccine (egg-derived seasonal trivalent, thiomersal free; eTIV_a).<br>* egg based trivalent influenza vaccine (eTIV_a) administered as 0.5 mL single dose in the deltoid muscle, preferably of the non-dominant arm.<br>|
| Experimental: FLU (cTIV or eTIV_a)<br>Cell culture derived seasonal trivalent influenza vaccine (cTIV) or influenza virus vaccine (egg-derived seasonal trivalent, thiomersal free; eTIV_a). | Biological: cTIV or eTIV_a<br>* 0.5 mL, Single dose of either cell cultured trivalent influenza vaccine (cTIV) or egg based trivalent influenza vaccine eTIV_a administered.<br>|
| Active Comparator: FLU (cTIV or eTIV_a) + PV<br>23-valent Pneumococcal vaccine (PV) concomitantly administered with cell culture derived seasonal trivalent influenza vaccine (cTIV) or influenza virus vaccine (egg-derived seasonal trivalent, thiomersal free; eTIV_a). | Biological: cTIV+PV OR eTIV_a+PV<br>* 0.5 mL, Single dose of either cell culture derived seasonal trivalent influenza vaccine (cTIV) or influenza virus vaccine (egg-derived seasonal trivalent, thiomersal free; eTIV_a) administered concomitantly with 23-valent pneumococcal polysaccharide vaccine (PV).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Randomized Participants Reporting Local and Systemic Reactions. | Safety and tolerability evaluation of influenza vaccines, within one week of single intramuscular injection. Local reactions reported for Influenza Vaccine Injection site. | One week postvaccination | 
| Immunogenicity Assessment by Geometric Mean Titers (GMT). | Non-inferiority of the influenza vaccine FLU (cell-culture derived seasonal trivalent influenza vaccine (cTIV); and influenza virus vaccine (egg-derived seasonal trivalent, thiomersal free; eTIV_a)) when administered alone versus administered concomitantly with pneumococcal vaccine (FLU + PV) is met if lower limit of the 2-sided 95% confidence interval (CI) of postvaccination (Day 22) Geometric Mean Titer ratio (FLU+PV/FLU) is greater than 0.5. | Three weeks postvaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Unrandomized Participants Reporting Local and Systemic Reactions. | Safety and tolerability evaluation of influenza vaccines, within one week of single intramuscular injection. | One week postvaccination | 
| Number of Randomized Participants Reporting Local and Systemic Reactions. | Safety and tolerability evaluation, within one week of single intramuscular injection of influenza vaccines (cell-culture derived seasonal trivalent influenza vaccine (cTIV) or influenza virus vaccine (egg-derived seasonal trivalent, thiomersal free; eTIV_a) when administered alone or concomitantly with a pneumococcal vaccine (PV)). Local reactions reported for Influenza Vaccine Injection Site. | One week postvaccination | 
| Number of Subjects With Antibody Response as Assessed by Hemagglutination Inhibition Assay. | Immunogenicity (seroconversion or significant increase in antibody titer and HI titer ≥1:40) of cell cultured and egg based trivalent influenza vaccine three weeks after a single injection, by the measurement of strain-specific hemagglutination inhibition (HI) tests according to the Committee for Medicinal Products for Human Use (CHMP) criteria (CPMP/BWP/214/96). Seroconversion was defined as negative pre-vaccination titer (<10)/postvaccination titer ≥40. Significant increase in antibody titer was defined as at least a fourfold increase from non-negative baseline (≥10). | Three weeks postvaccination | 
| Geometric Mean Ratio (GMR Day 22/Day1) After Single Dose of Influenza Vaccine. | Immunogenicity (geometric mean titer ratio) of cell cultured and egg based trivalent influenza vaccine three weeks after a single injection, by the measurement of strain-specific hemagglutination inhibition (HI) tests according to the CHMP criteria (CPMP/BWP/214/96). CHMP Criteria fulfilled if the Geometric Mean titer Ratio (GMR) is > 2.5. | Three weeks postvaccination |