A Study to Evaluate the Safety, Tolerability, Immunogenicity, and Lot Consistency of V116 in Adults 18 to 49 Years of Age (V116-004, STRIDE-4)

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, and immunogenicity of a pneumococcal 21-valent conjugate vaccine (V116) in pneumococcal vaccine-naïve adults 18 to 49 years of age. The primary study hypothesis is that all 3 lots of V116 are equivalent as assessed by the serotype-specific opsonophagocytic activity (OPA) Geometric Mean Titers (GMTs) at 30 days postvaccination for all serotypes included in V116.

Official Title
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A Phase 3 Randomized, Double-blind, Active Comparator-controlled, Lot-to-Lot Consistency Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Adults 18 to 49 Years of Age

Conditions
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Pneumococcal Disease

Intervention / Treatment
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* Biological: V116
* Biological: PPSV23


Participation Criteria
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Eligibility Criteria
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The key inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: Has underlying chronic conditions but assessed to be stable as per investigator Has ability to complete electronic Vaccine Report Card (eVRC) data collection without assistance as per investigator Exclusion Criteria: Has a history of invasive pneumococcal disease (IPD) or other culture-positive pneumococcal disease ≤3 years before Visit 1 (Day 1) Has a known or suspected congenital immunodeficiency, functional or anatomic asplenia, or history of autoimmune disease Has a coagulation disorder contraindicating intramuscular vaccination Has a recent illness with fever Has a known malignancy that is progressing or has required active treatment <3 years before enrollment Is expected to receive any pneumococcal vaccine during the study outside of the protocol Has received systemic corticosteroids for ≥14 consecutive days and has not completed treatment ≥14 days before receipt of study vaccine 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 study vaccine Has received any live vaccine ≤30 days before receipt of study vaccine or is scheduled to receive any live vaccine ≤30 days after receipt of study vaccine Has received a blood transfusion or blood products, including immunoglobulins ≤6 months before receipt of study vaccine or is scheduled to receive a blood transfusion or blood product ≤30 days after receipt of study vaccine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V116 Lot 1<br>Participants will receive a single 0.5 mL intramuscular (IM) dose of V116 Lot 1 on Day 1. | Biological: V116<br>* Pneumococcal 21-valent conjugate vaccine with 4 μg of each of the following 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;|
| Experimental: V116 Lot 2<br>Participants will receive a single 0.5 mL IM dose of V116 Lot 2 on Day 1. | Biological: V116<br>* Pneumococcal 21-valent conjugate vaccine with 4 μg of each of the following 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;|
| Experimental: V116 Lot 3<br>Participants will receive a single 0.5 mL IM dose of V116 Lot 3 on Day 1. | Biological: V116<br>* Pneumococcal 21-valent conjugate vaccine with 4 μg of each of the following 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: PPSV23<br>Participants will receive a single 0.5 mL IM dose of PPSV23 on Day 1. | Biological: PPSV23<br>* Pneumococcal 23-valent conjugate vaccine with 25 μg of each of the following 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;|

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 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs include pain/tenderness, redness/erythema, and swelling. | Up to  5 days | 
| Percentage of participants with solicited systemic AEs | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs include headache, muscle aches/myalgia, and tiredness/fatigue. | Up to  5 days | 
| Percentage of participants with vaccine-related serious adverse events (SAEs) | An 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  6 months | 
| Geometric mean titers (GMTs) of serotype-specific opsonophagocytic activity (OPA) for all serotypes in V116 following vaccination with 1 of 3 different lots of V116 | Serotype-specific OPA GMT for all serotypes in V116 following vaccination will be determined using multiplex opsonophagocytic assay (MOPA). | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMTs of serotype-specific OPA for all serotypes in V116 following vaccination: combined lots of V116 or PNEUMOVAX™ | Serotype-specific OPA GMT for all serotypes in V116 following vaccination will be determined using MOPA. | Day 30 | 
| Geometric mean concentrations (GMCs) of serotype-specific Immunoglobulin G (IgG) for all serotypes in V116 following vaccination with separate V116 lots | Serotype-specific IgG GMC for all serotypes in V116 following vaccination will be determined using pneumococcal electrochemiluminescence (PnECL). | Day 30 | 
| GMCs of serotype-specific IgG for all serotypes in V116 following vaccination: combined lots of V116 or PNEUMOVAX™ | Serotype-specific IgG GMC for all serotypes in V116 following vaccination will be determined using PnECL. | Day 30 | 
| Geometric mean fold rise (GMFR) in serotype-specific OPA for all serotypes in V116 following vaccination with separate V116 Lots | Serotype-specific OPA GMFR for all serotypes in V116 following vaccination will be determined using MOPA. | Baseline (Day 1) and Day 30 | 
| Percentage of participants with ≥4-fold rise in serotype-specific OPA for all serotypes in V116 following vaccination with separate V116 Lots | Percentage of participants with a ≥4-fold rise in serotype-specific OPA for all serotypes in V116 following vaccination will be reported. | Baseline (Day 1) and Day 30 | 
| GMFR in serotype-specific IgG for all serotypes in V116 following vaccination with separate V116 Lots | Serotype-specific IgG GMFR for all serotypes in V116 following vaccination will be determined using PnECL. | Baseline (Day 1) and Day 30 | 
| Percentage of participants with ≥4-fold rise in serotype-specific IgG for all serotypes in V116 following vaccination with separate V116 Lots | Percentage of participants with a ≥4-fold rise in serotype-specific IgG for all serotypes in V116 following vaccination will be reported. | Baseline (Day 1) and Day 30 | 
| GMTs of serotype-specific OPA for cross-reactive serotypes following vaccination with separate V116 Lots | Serotype-specific OPA GMTs for cross-reactive serotypes following vaccination will be determined using MOPA. | Day 30 |