Concomitant Administration of 13-valent Pneumococcal Conjugate Vaccine (13vPnC) With Influenza Vaccine in 23-valent Pneumococcal Polysaccharide (23vPS) Pre-vaccinated Adults.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity and safety of 13-valent pneumococcal polysaccharide vaccine when given concomitantly with seasonal inactivated influenza vaccine to adults 50 years and older who have previously received 23-valent pneumococcal polysaccharide vaccine.

Official Title
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A Phase 4, Randomized, Double-blind Trial To Evaluate The Immunogenicity And Safety Of A 13-valent Pneumococcal Conjugate Vaccine When Administered Concomitantly With Seasonal Inactivated Influenza Vaccine In Adults 50 Years And Older Who Received 1 Or More Doses Of 23-valent Pneumococcal Polysaccharide Vaccine Prior To Study Enrollment.

Conditions
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PREVENTION OF INVASIVE PNEUMOCOCCAL DISEASE

Intervention / Treatment
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* Biological: 13-valent pneumococcal conjugate vaccine
* Biological: Seasonal Inactivated Influenza Vaccine
* Other: Placebo
* Other: Placebo
* Biological: Seasonal Inactivated Influenza Vaccine
* Biological: 13-valent pneumococcal conjugate vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of a personally signed and dated informed consent document (ICD) indicating that the subject has been informed of all pertinent aspects of the study. Male or female adults 50 years of age or older. Documented vaccination with 1 or more prior doses of 23vPS, the last given at least 1 year prior to study enrollment. Negative urine pregnancy test for all female subjects who are of child bearing potential. Exclusion Criteria: Previous vaccination with Prevnar®, Prevnar 13®, or any other investigational pneumococcal conjugate vaccine. History of severe adverse reactions associated with any vaccine or vaccine-related component. Allergic to egg proteins (egg or egg products) and chicken proteins. History of Guillain-Barré syndrome. Vaccination with any influenza vaccine within 6 months (182 days) before investigational product administration. Documented S pneumoniae infection within the past 5 years before investigational product administration.

Ages Eligible for Study
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Minimum Age: 50 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: Basic Science
Allocation: Randomized
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 13vPnC+SIIV/Placebo<br> | Biological: 13-valent pneumococcal conjugate vaccine<br>* One (1) dose (0.5 mL) will be administered intramuscularly into the left deltoid either at Visit 1 or at Visit 2, depending on the randomization group assigned to the subject.<br>* Other names: 13vPnC;Biological: Seasonal Inactivated Influenza Vaccine<br>* One (1) dose of SIIV will be administered intramuscularly into the right deltoid of all subjects at Visit 1.<br>* Other names: SIIV;Other: Placebo<br>* One (1) dose (0.5 mL) will be administered intramuscularly into the left deltoid either at Visit 1 or at Visit 2, depending on the randomization group assigned to the subject.<br>|
| Other: Placebo+SIIV/13vPnC<br> | Other: Placebo<br>* One (1) dose (0.5 mL) will be administered intramuscularly into the left deltoid either at Visit 1 or at Visit 2, depending on the randomization group assigned to the subject.<br>Biological: Seasonal Inactivated Influenza Vaccine<br>* One (1) dose of SIIV will be administered intramuscularly into the right deltoid of all subjects at Visit 1.<br>* Other names: SIIV;Biological: 13-valent pneumococcal conjugate vaccine<br>* One (1) dose (0.5 mL) will be administered intramuscularly into the left deltoid either at Visit 1 or at Visit 2, depending on the randomization group assigned to the subject.<br>* Other names: 13vPnC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for 13 Pneumococcal Serotypes | Serotype-specific OPA GMTs for each of the 13 pneumococcal common serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were logarithmically transformed for analysis. Confidence intervals (CIs) for GMT were back-transformed based on the Student t distribution for the mean logarithm of the titers. GMTs were calculated using all participants with available data for the specified blood draw. Here, number of participants analyzed signifies the participants who were evaluable at this timepoint and n signifies participants with a determinate OPA titer to the given serotype. | 1 month after Vaccination 1 for 13vPnC+QIV/Placebo, 1 Month After Vaccination 2 for Placebo+QIV/13vPnC | 
| Hemagglutination Inhibition Assay (HAI) Geometric Mean Titers (GMTs) for Each Influenza Virus Strain in Quadrivalent Influenza Vaccine (QIV) | HAI GMTs were computed for assay titers collected 1 month after Vaccination 1 by vaccine sequence for each influenza virus strain (A/H1N1, A/H3N2, B/Brisbane and B/Massachusetts). CIs were back-transformations of a CI based on the Student t distribution for the mean logarithm of the titers. HAI GMTs were calculated using all participants with available data for the specified blood draw. Here, number of participants analyzed signifies participants with a determinate HAI titer to the given strain. | 1 month after Vaccination 1 | 
| Percentage of Participants With Treatment--Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) After Vaccination 1 | An AE was any untoward medical occurrence in a participant who received vaccine without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious adverse events (Non-SAEs). | Within 28 to 42 days after Vaccination 1 | 
| Percentage of Participants With Treatment--Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) After Vaccination 2 | An AE was any untoward medical occurrence in a participant who received vaccine without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious adverse events (Non-SAEs). | Within 28 to 42 days after Vaccination 2 | 
| Percentage of Participants With Treatment--Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) After 13vPnC Vaccination | An AE was any untoward medical occurrence in a participant who received vaccine without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious adverse events (Non-SAEs). | Baseline (Vaccination 1) up to 28 to 42 Days after Vaccination 2 | 
| Percentage of Participants With Treatment--Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) at the 6-Month Follow-up | An AE was any untoward medical occurrence in a participant who received vaccine without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious adverse events (Non-SAEs). | Within 168 to 196 days after Vaccination 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) Antibody Titer Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) | Percentage of participants achieving predefined OPA antibody titer >= LLOQ for each of the 13 pneumococcal serotypes (LLOQs for each serotype OPA were set as- serotype 1: 18; serotype 3: 12; serotype 4: 21; serotype 5: 29; serotype 6A: 37; serotype 6B: 43; serotype 7F: 210; serotype 9V: 345; serotype 14: 35; serotype 18C: 31; serotype 19A: 18; serotype 19F: 48; and serotype 23F: 13) determined in blood samples of all participants were calculated. Exact, 2-sided 95% CIs based on the observed percentage of participants were determined by using Clopper and Pearson method. OPA titers were calculated using all participants with available data from 1 month after 13vPnC vaccination blood draw. Here, number of participants analyzed signifies the participants who were evaluable at this timepoint and n signifies participants with valid and determinate assay results to the specified serotype. | 1 Month After Vaccination 1 for 13vPnC+QIV/Placebo, 1 month after Vaccination 2 for Placebo+QIV/13vPnC | 
| Geometric Mean Fold Rise (GMFR) for Pneumococcal Serotype-Specific Opsonophagocytic Activity (OPA) Titers 1 Month After 13vPnC Vaccination 1 to Immediately Before 13vPnC Vaccination 1 | GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) 1 month after Vaccination 1 to before Vaccination 1 were computed using the logarithmically transformed assay results. CIs for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both before Vaccination 1 and 1 month after Vaccination 1 blood draws. Here, n signifies participants with valid and determinate assay results for specified serotype at both the given visits. Number of participants who received at least 1 dose of 13vPnC during Vaccination 1 were analyzed. | Immediately before Vaccination 1, 1 month after Vaccination 1 | 
| Geometric Mean Fold Rise (GMFR) for Pneumococcal Serotype-Specific Opsonophagocytic Activity (OPA) Titers 1 Month After 13vPnC Vaccination 2 to Immediately Before 13vPnC Vaccination 2 | GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) 1 month after Vaccination 2 to before Vaccination 2 (1 month after Vaccination 1) were computed using the logarithmically transformed assay results. CIs for GMFR were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all participants with available data from both before Vaccination 2 and 1 month after Vaccination 2 blood draws. Here, number of participants analyzed signifies total participants who were evaluable at this timepoint and n signifies participants with valid and determinate assay results for specified serotype at both the given visits. Number of participants who received at least 1 dose of 13vPnC during Vaccination 2 were analyzed. | Immediately before Vaccination 2, 1 month after Vaccination 2 | 
| Percentage of Participants Achieving Seroconversion in Hemagglutination Inhibition Assay (HAI) Titers | Percentage of participants achieving seroconversion in HAI titers was defined as the percentage of participants with either before Vaccination 1 (pre-vaccination 1) HAI titer less than <1:10 and after Vaccination 1 (post-vaccination 1) HAI titer >=1:40 or before Vaccination 1 (pre-vaccination 1) HAI titer >=1:10 and a minimum 4-fold rise in after Vaccination 1 (post-vaccination 1) HAI antibody titer with respect to before Vaccination 1 (pre-vaccination) titer for influenza virus strains. Here, number of participants analyzed signifies the participants who were evaluable at this timepoint. | Immediately before Vaccination 1, 1 month after Vaccination 1 | 
| Geometric Mean Fold Rise (GMFR) in Hemagglutination Inhibition Assay (HAI) 1 Month After Vaccination 1 to Immediately Before Vaccination 1 | Fold rise 1 month after Vaccination 1 to before Vaccination 1 was calculated for each influenza virus strain (A/H1N1, A/H3N2, B/Brisbane and B/Massachusetts). GMFRs were calculated using all participants with available data from both the specified blood draws. CI for the GMFRs were back transformations of a CI based on the Student t distribution for mean fold rise. Here, number of participants analyzed signifies participants with valid and determinate assay results for specified strain at both the specified blood draws. | Immediately before Vaccination 1, 1 month after Vaccination 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumococcal polysaccharide vaccine, 13-valent pneumococcal conjugate vaccine, invasive pneumococcal disease, flu vaccine