Immunogenicity and Safety of PCV13 and Fluad in Adults Aged ≥60 Years

Study Overview
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Brief Summary
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Recent reviews have highlighted the unpredictability and complexity of immune interference when multivalent conjugate vaccines are co-administered with other pediatric vaccines. It has become evident that the likelihood of immune interference (in response to conjugated- or co-administered antigens) increases in proportional to the number of glyco-conjugates (valencies) and dosages of carrier proteins. There are many kinds of carrier proteins: tetanus toxoid (TT), diphtheria toxoid (DT), CRM197 (non-toxic variant of DT), OMP (complex outer-membrane protein mixture from Neisseria meningitidis) and non-typeable Hemophilus influenza-derived protein D. Among them, TT is a more potent inducer of T-helper immunity, but carrier-induced-epitopic suppression (dose-dependent carrier antibody and carrier B cell dominance) may occur with TT. In comparison, DT and CRM197 are weaker B-cell immunogens, but apparently trigger more T-regulatory mechanism. Recent pediatric studies of PCV13 co-administered with DTaP vaccines showed 6B GMT (geometric mean titer) to be somewhat reduced compared to the results with PCV13 alone. 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. PCV13 has limited co-administration information for adjuvanted influenza vaccine. This study is designed to evaluate the immunogenicity and safety of PCV13 and MF59-adjuvanted influenza vaccine (Fluad) after concomitant administration in adults aged 60 years or older.

Detailed Description
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This study is a multi-centered, randomized controlled clinical trial: Korea University Guro Hospital, Korea University Ansan Hospital, Hallym University Gangnam Sacred Hospital and Catholic University Medical College, St. Vincent's Hospital. The primary objective is to evaluate the immunogenicity of Fluad after concomitant administration of Fluad and PCV13 in adults aged 60 years or more. This study is designed to demonstrate non-inferiority of sero-conversion rate after Fluad vaccination: Fluad-PCV13 co-administration group versus Fluad alone group The secondary objective is to evaluate the immunogenicity of PCV13 after concomitant administration in adults aged 60 years or more. This study is designed to demonstrate non-inferiority of PCV13 when co-administered with Fluad compared with PCV13 alone. This study is also designed to evaluate the safety of concomitant PCV13-Fluad administration in adults aged 60 years or more. All the participants will be followed for the duration of an expected average of 4 weeks after vaccination.

Official Title
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Immunogenicity and Safety of 13-valent Pneumococcal Conjugate Vaccine (PCV13) and MF59-adjuvanted Influenza Vaccine (Fluad) After Concomitant Vaccination in Adults Aged ≥60 Years

Conditions
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Influenza, Streptococcus Pneumoniae

Intervention / Treatment
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* Biological: Fluad and Prevenar13
* Biological: Fluad
* Biological: Prevenar13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged ≥60 years who signed the informed consent Exclusion Criteria: Previous pneumococcal vaccine recipients Egg allergy History of serious adverse event after vaccination, any acute disease or infection History of neurological symptoms or signs Impairment of immune function or immunosuppressant use Bleeding diathesis Fever (defined as axillary temperature ³38.0°C) within 3 days (prior to Visit 1)

Ages Eligible for Study
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Minimum Age: 60 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: PCV13 and Fluad<br>437 concomitant Fluad-PCV13 recipients: one dose of each vaccine administered on Day 0 | Biological: Fluad and Prevenar13<br> <br> |
| Active Comparator: Fluad alone<br>437 Fluad recipients: one vaccine injection administered on Day 0 | Biological: Fluad<br> <br> |
| Active Comparator: PCV13 alone<br>437 PCV13 recipients: one vaccine injection administered on Day 0 | Biological: Prevenar13<br> <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 and GMT folds (A/H1N1, A/H3N2, and B) | Seroprotection rate: percentage of subjects with a post-vaccination titer ≥1:40 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 PCV13 | OPA geometric mean titers for 13 PCV13 serotypes with corresponding 2-sided 95% confidence intervals between groups receiving PCV 13 and then compare the results | Outcome measure will be assessed at two points (baseline and 4 weeks after vaccination). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, Safety, MF59, Influenza vaccine, Pneumococcal vaccine