Study Comparing a 13-valent Pneumococcal Conjugate Vaccine With 23-valent Pneumococcal Polysaccharide Vaccine in Adults

Study Overview
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Brief Summary
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This study will assess the safety, tolerability and immune response of 13-valent pneumococcal conjugate vaccine (13vPnC) compared with 23-valent Pneumococcal Polysaccharide Vaccine (23vPS). Although the study started with only 1 population, amendments to the original protocol will now reflect three participant populations. Three age cohorts will be enrolled. The first cohort (age 60-64) will be blinded. Cohort 2 (age 50-59) and cohort 3 (age 18-49) are open label. Subjects in cohorts 1 and 2 will receive 2 vaccinations 3-4 years apart. Subjects in cohort 3 will receive 1 vaccination. All participants should be naïve of 23vPS. Comparisons of immune responses from the different cohorts will be done.

Official Title
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A Phase 3, Randomized, Active-controlled, Modified Double-blind Trial Evaluating The Safety, Tolerability, And Immunogenicity Of A 13-valent Pneumococcal Conjugate Vaccine (13vpnc) Compared To A 23-valent Pneumococcal Polysaccharide Vaccine (23vps) In Adults 60 To 64 Years Old Who Are Naive To 23vps And The Safety, Tolerability, And Immunogenicity Of 13vpnc In Adults 18-59 Years Old Who Are Naïve To 23vps

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: 13-valent pneumococcal conjugate vaccine (13vPnC)
* Biological: 23-valent Pneumococcal Polysaccharide Vaccine (23vPS)
* Biological: 13-valent pneumococcal conjugate vaccine (13vPnC)
* Biological: 13-valent pneumococcal conjugate vaccine (13vPnC)
* Biological: 13-valent pneumococcal conjugate vaccine (13vPnC)
* Biological: 23-valent Pneumococcal Polysaccharide Vaccine (23vPS)
* Biological: 13-valent pneumococcal conjugate vaccine (13vPnC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First Cohort: Healthy Male and female adults 60 to 64 years of age at time of enrollment. Second Cohort: Healthy Male and female adults 50 to 59 years of age at time of enrollment. Third Cohort: Healthy Male and female adults 18 to 49 years of age at time of enrollment. Exclusion Criteria: Previous immunization with any licensed or experimental pneumococcal vaccine. Serious chronic disorders including metastatic malignancy, severe chronic obstructive pulmonary disease (COPD) requiring supplemental oxygen, end stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder which in the investigator's opinion precludes the subject from participating in the study. Known or suspected impairment of immunological function.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 13vPnC Cohort 1, Vaccination 1<br>Participants aged 60-64 years were given a 0.5 mL dose administered on day 1. | Biological: 13-valent pneumococcal conjugate vaccine (13vPnC)<br>* 0.5 mL dose administered on day 1<br>|
| Active Comparator: 23vPS Cohort 1, Vaccination 1<br>Participants aged 60-64 years were given a 0.5 mL dose administered on day 1. | Biological: 23-valent Pneumococcal Polysaccharide Vaccine (23vPS)<br>* 0.5 mL dose administered on day 1<br>|
| Experimental: 13vPnC Cohort 2, Vaccination 1<br>Participants aged 50-59 years given a 0.5 mL dose administered on day 1. | Biological: 13-valent pneumococcal conjugate vaccine (13vPnC)<br>* 0.5 mL dose administered on day 1<br>|
| Experimental: 13vPnC Cohort 3, Vaccination 1<br>Participants aged 18-49 years given a 0.5 mL dose administered on day 1. | Biological: 13-valent pneumococcal conjugate vaccine (13vPnC)<br>* 0.5 mL dose administered on day 1<br>|
| Experimental: 13vPnC Cohort 1, Vaccination 2<br>Participants aged 60-64 years who received 13vPnC at vaccination 1 receive a 0.5 mL dose of 13vPnC administered 3-4 years after dose 1. | Biological: 13-valent pneumococcal conjugate vaccine (13vPnC)<br>* 0.5 mL dose administered 3-4 years after dose 1<br>|
| Active Comparator: 23vPS Cohort 1, Vaccination 2<br>Participants aged 60-64 years who received 23vPS at vaccination 1 receive a 0.5 mL dose of 23vPS administered 3-4 years after dose 1. | Biological: 23-valent Pneumococcal Polysaccharide Vaccine (23vPS)<br>* 0.5 mL dose administered 3-4 years after dose 1<br>|
| Experimental: 13vPnC Cohort 2, Vaccination 2<br>Participants aged 50-59 years who received 13vPnC at vaccination 1 receive a 0.5 mL dose of 13vPnC administered 3-4 years after dose 1. | Biological: 13-valent pneumococcal conjugate vaccine (13vPnC)<br>* 0.5 mL dose administered 3-4 years after dose 1<br>|

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) 1 Month After Vaccination 1 | Serotype-specific OPA GMTs for the 13 pneumococcal common serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of all the participants using microcolony OPA (mcOPA) assay. CIs for GMT are back transformations of a CI based on the Student t distribution for the mean logarithm of the titers. | One month after vaccination 1 | 
| Percentage of Participants Achieving At Least a 4-fold Rise in OPA Titer for Serotype 6A 1 Month After Vaccination 1 in Cohort 1 | For serotype 6A the percentage of participants achieving at least a 4-fold rise on the serotype-specific antibody titer from pre-vaccination to 1 month post-vaccination was computed along with exact, 2-sided 95% confidence interval for the proportion. | One month after vaccination 1 | 
| Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) 1 Month After Vaccination for 12 Common Serotypes in 13vPnC/23vPS Group Relative to 23vPS Group and 23vPS/23vPS Group | Serotype-specific OPA GMTs for the 12 pneumococcal common serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were determined in the blood samples of all the participants using mcOPA assay. CIs for GMT are back transformations of a CI based on the Student t distribution for the mean logarithm of the titers. | One month after vaccination 1 and One month after vaccination 2/Year 3 to 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving OPA Titers With at Least Lower Limit of Quantification (LLOQ) 1 Month After Vaccination 1 | Percentage of participants achieving OPA GMTs with at least LLOQ for 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) determined in blood samples of all participants using mcOPA assay. Exact 2-sided CI based on observed proportion of participants. LLOQ for each serotype: 1=1:18, 3=1:12, 4=1:21, 5=1:29, 6A=1:37, 6B=1:43, 7F=1:210, 9V=1:345, 14=1:35, 18C=1:31, 19A=1:18, 19F=1:48, 23F=1:13. | One month after vaccination 1 | 
| Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rises (GMFRs) for the 13 Serotypes From Prevaccination 1 to 1 Month After Vaccination 2 in Cohort 1 and Cohort 2 | Geometric mean fold rises (GMFRs) for the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from prevaccination to 1 month postvaccination were computed using the logarithmically transformed assay results. CI for the GMFRs are back transformations of a CI based on the Student t distribution for the logarithmically transformed assay results. | Prevaccination 1 to 1 month after vaccination 2/Year 3 to 4 | 
| Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) for 12 Common Serotypes in 13vPnC/23vPS Group Relative to 23vPS and 23vPS/23vPS Groups in Cohort 1; and in 13vPnC/13vPnC Group in Cohort 2, 1 Month After Vaccination | Antibody geometric mean concentration (GMC) as measured by microgram/milliliter (mcg/mL) for 12 common pneumococcal serotypes (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) are presented. GMC and corresponding 2-sided 95% confidence intervals (CI) were evaluated. Geometric means (GMs) were calculated using all participants with available data for the specified blood draw. | One month after vaccination 1 and One month after vaccination 2/Year 3 to 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Pneumococcal Infections Prevention and Control