Trial to Evaluate the Safety and Immunogenicity of a 20-Valent Pneumococcal Vaccine in Adults 65 Years of Age or Older With Prior Pneumococcal Vaccination

Study Overview
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Brief Summary
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This Phase 3 will describe the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine formulation in adults 65 years of age or older with prior pneumococcal vaccination

Official Title
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A PHASE 3, RANDOMIZED, OPEN-LABEL TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN ADULTS ≥65 YEARS OF AGE WITH PRIOR PNEUMOCOCCAL VACCINATION

Conditions
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Pneumococcal Disease

Intervention / Treatment
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* Biological: 13vPnC
* Biological: PPSV23
* Biological: 20vPnC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female adults 65 years of age or greater. Adults determined by clinical assessment, including medical history and clinical judgment, to be eligible for the study, including adults with preexisting stable disease, defined as disease not requiring significant change in therapy in the previous 6 weeks or hospitalization for worsening disease within 12 weeks before receipt of investigational product. Female subject of nonchildbearing potential; male subject not able to father children or who is able to father children and willing to use a highly effective method of contraception. Male or female adults who meet 1 of the following: Vaccination with PPSV23 greater than or equal to 1 year and less than or equal to 5 years prior to vaccination in the study, and no prior 13vPnC vaccination (Cohort A). Vaccination with 13vPnC greater than or equal to 6 months prior to vaccination in the study, and no prior PPSV23 vaccination (Cohort B). Vaccination with 13vPnC followed by PPSV23 (PPSV23 vaccination greater than or equal to 1 year prior to vaccination in the study) (Cohort C). Exclusion Criteria Serious chronic disorder 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 that, in the investigator's opinion, excludes the subject from participating in the study. History of microbiologically proven invasive disease caused by S pneumoniae.

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: 13vPnC<br>Pneumococcal conjugate vaccine | Biological: 13vPnC<br>* Pneumococcal conjugate vaccine<br>|
| Active Comparator: PPSV23<br>Pneumococcal polysaccharide vaccine | Biological: PPSV23<br>* Pneumococcal polysaccharide vaccine<br>|
| Experimental: 20vPnC<br>Pneumococcal conjugate vaccine | Biological: 20vPnC<br>* Pneumococcal conjugate vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Local reactions were recorded using an electronic diary (e-diary). Local reactions included redness, swelling and pain at the injection site. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm). Redness and swelling were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm) and severe (>10.0 cm). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity). | Within 10 days after vaccination | 
| Percentage of Participants With Systemic Events Within 7 Days After Vaccination | Systemic events fever, fatigue, headache, muscle pain and joint pain were recorded by using an e-diary. Fever was defined as temperature >=38.0 degree Celsius (C) and categorized to >=38.0 to 38.4 degree C, >38.4 to 38.9 degree C, >38.9 to 40.0 degree C and >40.0 degree C. Fatigue, headache, muscle pain and joint pain were graded as mild (did not interfere with activity), moderate (some interference with activity) and severe (prevented daily routine activity). | Within 7 days after vaccination | 
| Percentage of Participants With Adverse Events (AEs) Within 1 Month After Vaccination | An AE was any untoward medical occurrence in study participants who received study vaccine without regard to possibility of causal relationship with the treatment. | Within 1 month after vaccination | 
| Percentage of Participants With Serious Adverse Events (SAEs) Within 6 Months After Vaccination | An SAE was any untoward medical occurrence at any dose that results in death; is life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect or that is considered to be an important medical event. | Within 6 months after vaccination | 
| Percentage of Participants With Newly Diagnosed Chronic Medical Conditions (NDCMCs) Within 6 Months After Vaccination | An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or was otherwise long-lasting in its effects. | Within 6 months after vaccination | 
| Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) at 1 Month After Vaccination | OPA GMTs were determined for serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F. OPA titer was expressed as reciprocal of the highest serum dilution. | 1 month after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pneumococcal OPA Geometric Mean Fold Rise (GMFR) From Before Vaccination to 1 Month After Vaccination | OPA GMFR is the ratio of OPA GMTs, 1 month after vaccination to before vaccination. OPA GMFRs from before to 1 month after vaccination were calculated for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F. | From before vaccination to 1 month after vaccination | 
| Percentage of Participants With >=4-Fold Rise in Pneumococcal OPA Titers From Before Vaccination to 1 Month After Vaccination | Percentage of participants with a >=4-fold rise in pneumococcal OPA titers from before vaccination to 1 month after vaccination were calculated for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F. | From before vaccination to 1 month after vaccination | 
| Percentage of Participants With Pneumococcal OPA Titers >=Lower Limit of Quantitation (LLOQ) at 1 Month After Vaccination | The percentage of participants with OPA titers >=LLOQ at 1 month after vaccination were calculated for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F. | 1 month after vaccination |