MF59-adjuvanted Influenza Vaccine and 23-valent Pneumococcal Polysaccharide Vaccine

Study Overview
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Brief Summary
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Similar to children, adults frequently visit outpatient clinics to get two or more kinds of vaccines at the same time: pneumococcal vaccine, influenza vaccine, Td (diphtheria and tetanus) vaccine, HPV (human papilloma virus) vaccine, meningococcal vaccine, zoster vaccine, etc. This study is intended to evaluate the immunogenicity and safety of concomitant administration of 23-valent pneumococcal polysaccharide vaccine (PPV23, Prodiax) and MF59 adjuvanted trivalent influenza vaccine in the elderly subjects aged ≥65 years.

Detailed Description
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During influenza season, concomitant influenza and pneumococcal vaccination would be an effective strategy to enhance pneumococcal vaccine coverage rate in high-risk adults. However, the immunogenicity and safety of concomitant vaccination need to be further investigated. There is data on immunogenicity and safety after concomitant administration of pneumococcal polysaccharide vaccine (PPV) and unadjuvanted influenza vaccine; no interference was noted between two vaccines. However, there are no data for MF59 adjuvanted influenza vaccine with pneumococcal vaccine. MF59 only locally reacts for immune response, so immunogenicity should be assessed for both vaccines injected in same arm versus different arms. This study is intended to evaluate the immunogenicity and safety of concomitant MF59-adjuvanted trivalent influenza vaccine (MF59-aTIV, Fluad) and 23-valent pneumococcal polysaccharide vaccine (PPV23, Prodiax) vaccination in the elderly subjects aged ≥65 years. Healthy elderly subjects (N = 424) are randomized in a 1:1:1:1 ratio to receive MF59-aTIV alone (group 1), MF59-aTIV +PPV23 at different arm (group 2), MF59-aTIV +PPV23 at same arm (group 3) or PPV23 alone (group 4). Hemagglutination inhibition (HI) assay and multiplex opsono-phagocytic killing assay (MOPA) will be used to compare the immunogenicity of each vaccine after single or concomitant vaccination at pre-vaccination and 1 month post-vaccination. MOPA will be taken for four serotypes (5, 6B, 18C and 19A).

Official Title
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Immunogenicity and Safety of MF59-adjuvanted Trivalent Influenza Vaccine (Fluad) and 23-valent Pneumococcal Polysaccharide Vaccine (PPV23) in the Elderly: Single Versus Concomitant Vaccination

Conditions
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Influenza, Human, Pneumococcal Infections

Intervention / Treatment
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* Biological: Fluad alone
* Biological: Fluad and PPV23 on the different arms
* Biological: Fluad and PPV23 on the same arm
* Biological: PPV23 alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 65 years of age who are eligible for the study vaccines; Who have given written informed consent at the time of enrollment); Those who are available for all the visits scheduled in the study; Subjects In good health as determined by medical history, physical examination and clinical judgment of the investigator Exclusion Criteria: History of egg allergy History of influenza vaccination in previous 6 months History of any pneumococcal vaccination Documented S. pneumonia infection in the previous 5 years Chemotherapy for malignancy within the past 30 days High-dose systemic steroid (prednisone ≥0.5 mg/kg/day) in the past 30 days Receipt of blood product within 6 months before enrollment Significant acute or chronic infection within the previous 7 days or fever within the previous day Any serious chronic or progressive disease Any condition that might interfere with the study results.

Ages Eligible for Study
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Minimum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fluad alone<br>56 Fluad recipients: one vaccine injection administered on Day 0 | Biological: Fluad alone<br>* Fluad<br>|
| Active Comparator: Fluad and PPV23 on the different arms<br>56 concomitant Fluad-PPV23 recipients on the different arms: one dose of each vaccine administered on Day 0 | Biological: Fluad and PPV23 on the different arms<br>* Fluad and Prodiax<br>|
| Active Comparator: Fluad and PPV23 on the same arm<br>56 concomitant Fluad-PPV23 recipients on the same arm with 1 inch distance: one dose of each vaccine administered on Day 0 | Biological: Fluad and PPV23 on the same arm<br>* Fluad and Prodiax<br>|
| Active Comparator: PPV23 alone<br>56 PPV23 recipients: one vaccine injection administered on Day 0 | Biological: PPV23 alone<br>* Prodiax<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rates (A/H1N1, A/H3N2, and B) | a post-vaccination titer ≥1:40 in subjects with a pre-vaccination titer of <1:10 or a ≥4-fold titer increase in subjects with a pre-vaccination titer of ≥1:10 | Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection rates (A/H1N1, A/H3N2, and B) | Percentage of subjects with a post-vaccination titer ≥1:40 | Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination). | 
| GMT folds (A/H1N1, A/H3N2, and B) | GMT-fold change: GMT ratio of the post-vaccination titer to pre-vaccination titer | Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination. | 
| Opsonophagocytic assay (OPA) titers for four serotypes of PPV23 (serotypes 5, 6B, 18C and 19A) | OPA geometric mean titers for four PPV23 serotypes with corresponding 2-sided 95% confidence intervals will be compared between groups receiving PPV23: MF59-adjuvanted TIV + PPV23 at different arm, MF59-adjuvanted TIV + PPV23 at same arm and PPV23 alone. | Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination). |