A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine-experienced Adults (V116-006, STRIDE-6)

Study Overview
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Brief Summary
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This a study of V116 in adults ≥50 years of age who previously received a pneumococcal vaccination ≥1 year before enrollment. The primary objectives of this study are to evaluate the safety, tolerability, and immunogenicity of V116.

Detailed Description
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Participants will be randomized to 1 of 3 cohorts depending upon prior vaccinations. Prior vaccinations by cohort include: PPSV23 (pneumococcal vaccine, polyvalent [23-valent], PNEUMOVAX™23) for Cohort 1; PCV13 (pneumococcal 13-valent conjugate vaccine; PREVNAR 13™) for Cohort 2; PCV15 (pneumococcal 15-valent conjugate vaccine; VAXNEUVANCE™), PCV20 (pneumococcal 20-valent conjugate vaccine; PREVNAR 20™), PCV13+PPSV23, PCV15+PPSV23, or PPSV23+PCV13 for Cohort 3.

Official Title
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A Phase 3 Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine-Experienced Adults 50 Years of Age or Older

Conditions
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Pneumonia, Pneumococcal

Intervention / Treatment
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* Biological: V116
* Biological: PCV15
* Biological: PPSV23


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has received pneumococcal vaccine >= 1 year before enrollment (PCV13, PCV15, PCV20, PPSV23, PCV13+PPSV23, PPSV23+PCV13, or PCV15+PPSV23). Exclusion Criteria: Has a history of invasive pneumococcal disease (IPD). Has a known hypersensitivity to any component of V116, PCV15, PCV20, or PPSV23, including diphtheria toxoid. Has a known or suspected impairment of immunological function including, but not limited to, a history of congenital or acquired immunodeficiency, documented human immunodeficiency virus (HIV) infection, functional or anatomic asplenia, or history of autoimmune disease. Has a coagulation disorder contraindicating intramuscular vaccination. Has a known malignancy that is progressing or has required active treatment. Has received PPSV23 followed by either PCV15 or PCV20. Received systemic corticosteroids (prednisone equivalent of ≥20 mg/day). Is currently receiving immunosuppressive therapy, including chemotherapeutic agents or other immunotherapies/immunomodulators used to treat cancer or other conditions, and interventions associated with organ or bone marrow transplantation, or autoimmune disease. Has received any non-live vaccine ≤14 days before receipt of study vaccine or is scheduled to receive any non-live vaccine ≤30 days after receipt of any study vaccine. Has received any live virus vaccine ≤30 days before receipt of study vaccine or is scheduled to receive any live virus vaccine ≤30 days after receipt of study vaccine. Has received a blood transfusion or blood products, including immunoglobulin ≤6 months before receipt of study vaccine or is scheduled to receive a blood transfusion or blood product until the Day 30 post-vaccination blood draw is complete.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: V116<br>Participants will receive a single 0.5 mL intramuscular (IM) injection of V116 on Day 1. Participants in this arm received PPSV23 prior to the enrollment. | Biological: V116<br>* Pneumococcal 21-valent conjugate vaccine with 4 μg of each of the pneumococcal polysaccharides (PnPs) antigen: 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B in each 0.5 mL sterile solution<br>* Other names: Pneumococcal 21-valent Conjugate Vaccine;|
| Active Comparator: Cohort 1: PCV15<br>Participants will receive a single 0.5 mL IM injection of PCV15 on Day 1. Participants in this arm received PPSV23 prior to the enrollment. | Biological: PCV15<br>* Pneumococcal 15-valent conjugate vaccine with 2 μg of each of the PnPs antigen: 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F, and 4 μg of 6B in each 0.5 mL sterile solution<br>* Other names: VAXNEUVANCE™;|
| Experimental: Cohort 2: V116<br>Participants will receive a single 0.5 mL IM injection of V116 on Day 1. Participants in this arm received PCV13 prior to the enrollment. | Biological: V116<br>* Pneumococcal 21-valent conjugate vaccine with 4 μg of each of the pneumococcal polysaccharides (PnPs) antigen: 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B in each 0.5 mL sterile solution<br>* Other names: Pneumococcal 21-valent Conjugate Vaccine;|
| Active Comparator: Cohort 2: PPSV23<br>Participants will receive a single 0.5 mL IM injection of PPSV23 on Day 1. Participants in this arm received PCV13 prior to the enrollment. | Biological: PPSV23<br>* Pneumococcal 23-valent vaccine with 25 μg of each of the PnPs antigen: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F in each 0.5 mL sterile solution<br>* Other names: PNEUMOVAX™23;|
| Experimental: Cohort 3: V116<br>Participants will receive a single 0.5 mL IM injection of V116 on Day 1. Participants in this arm received PCV15, PCV20, PCV13+PPSV23, PCV15+PPSV23, or PPSV23+PCV13 prior to the enrollment. | Biological: V116<br>* Pneumococcal 21-valent conjugate vaccine with 4 μg of each of the pneumococcal polysaccharides (PnPs) antigen: 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B in each 0.5 mL sterile solution<br>* Other names: Pneumococcal 21-valent Conjugate Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Solicited Injection-site Adverse Events (AEs) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The solicited injection-site AEs include tenderness/injection-site pain, injection-site redness/injection-site erythema, and injection-site swelling/injection-site swelling. | Up to 5 days post-vaccination | 
| Percentage of Participants with Solicited Systemic AEs | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The solicited systemic AEs include muscle aches all over body/myalgia, headache, and tiredness/fatigue. | Up to 5 days post-vaccination | 
| Percentage of Participants with Vaccine-related Serious Adverse Events (SAEs) | A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. SAEs that were reported to be at least possibly related by the investigator to study vaccination will be summarized. | Up to  180 days | 
| Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity (OPA) Responses | Opsonophagocytic activity (OPA) for the serotypes in V116 will be determined using a multiplexed opsonophagocytic assay (MOPA). | 30 Days post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) | The GMC of serotype-specific IgG for the serotypes contained in V116 (serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B) will be determined using an pneumococcal electrochemiluminescence (Pn ECL) assay. | 30 Days post-vaccination | 
| Geometric Mean Fold Rise (GMFR) of Serotype-specific OPA | Activity for the serotypes contained in V116 (serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B) will be determined using a MOPA. GMFR is defined as the geometric mean of the ratio of concentration at Day 30 after vaccination divided by concentration at baseline. | Day 1 (Baseline) and 30 days post-vaccination | 
| Geometric Mean Fold Rise (GMFR) of Serotype-specific IgG | Activity for the serotypes contained in V116 (serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B) will be determined using an Pn ECL assay. GMFR is defined as the geometric mean of the ratio of concentration at Day 30 after vaccination divided by concentration at baseline. | Baseline (Day 1) and 30 days post-vaccination |