Safety and Immunogenicity of V116 in Pneumococcal Vaccine-naïve Adults (V116-003, STRIDE-3)

Study Overview
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Brief Summary
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This is a phase 3, randomized, double-blind, active comparator-controlled study of the safety, tolerability, and immunogenicity of V116 compared to PCV20 (pneumococcal 20-valent conjugate vaccine ([Prevnar 20™ / APEXXNAR™]) in pneumococcal vaccine-naïve adults. It is hypothesized that V116 is noninferior to PCV20 for the common serotypes and superior to PCV20 for the unique serotypes as assessed by serotype specific opsonophagocytic activity (OPA) 30 days postvaccination. It is also hypothesized that V116 in participants 18 to 49 years of age immunobridges to V116 in participants 50 to 64 years of age as assessed by serotype specific OPA geometric mean titers (GMTs) 30 days postvaccination for all 21 serotypes in V116. Participants ≥50 years of age will be enrolled in Cohort 1, and participants 18 to 49 years of age will be enrolled in Cohort 2.

Official Title
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A Phase 3, Randomized, Double-blind, Active Comparator-controlled Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine-naïve Adults

Conditions
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Pneumococcal Infection

Intervention / Treatment
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* Biological: V116
* Biological: PCV20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For females, is not pregnant or breastfeeding and is either not a woman of childbearing potential (WOCBP) or is a WOCBP and uses acceptable contraception/abstinence; and has medical, menstrual, and recent sexual activity history reviewed by the investigator to decrease the chance of an early undetected pregnancy. Exclusion Criteria: Has a history of invasive pneumococcal disease (IPD) [positive blood culture, positive cerebrospinal fluid culture, or positive culture at another sterile site] or known history of other culture-positive pneumococcal disease within 3 years of Visit 1 (Day 1) Has a known hypersensitivity to any component of V116 or PCV20, 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 IM vaccination Had a recent febrile illness (defined as oral or tympanic temperature ≥100.4°F [≥38.0°C] or axillary or temporal temperature ≥99.4°F [≥37.4°C]) or received antibiotic therapy for any acute illness occurring <72 hours before receipt of study vaccine Has a known malignancy that is progressing or has required active treatment <3 years before enrollment Received prior administration (prior to age of 5 is acceptable) of any pneumococcal vaccine or is expected to receive any pneumococcal vaccine during the study outside the protocol Received systemic corticosteroids (prednisone equivalent of ≥20 mg/day) for ≥14 consecutive days and has not completed intervention ≥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 Received any nonlive vaccine ≤14 days before receipt of study vaccine or is scheduled to receive any nonlive vaccine ≤30 days after receipt of study vaccine (inactivated influenza and SARS-CoV2 vaccines may be acceptable) 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 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 postvaccination blood draw is complete

Ages Eligible for Study
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Minimum Age: 18 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>Pneumococcal vaccine-naïve adult participants (≥50 years of age) receive a single dose of V116 on Day 1. | Biological: V116<br>* 0.5 mL injection solution in prefilled syringe containing 4 μg of each PnPs antigen (3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B) given by intramuscular (IM) injection.<br>* Other names: Pneumococcal 21-valent Conjugate Vaccine;|
| Active Comparator: Cohort 1 PCV20<br>Pneumococcal vaccine-naïve adult participants (≥50 years of age) receive a single dose of PCV20 on Day 1. | Biological: PCV20<br>* 0.5 mL injection suspension in prefilled syringe containing 2.2 μg of each PnPs antigen (1, 3, 4, 5, 6A, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, 33F) and 4.4 μg of PnPs antigen 6B.<br>* Other names: APEXXNAR™;|
| Experimental: Cohort 2 V116<br>Pneumococcal vaccine-naïve adult participants (18 to 49 years of age) receive a single dose of V116 on Day 1. | Biological: V116<br>* 0.5 mL injection solution in prefilled syringe containing 4 μg of each PnPs antigen (3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B) given by intramuscular (IM) injection.<br>* Other names: Pneumococcal 21-valent Conjugate Vaccine;|
| Active Comparator: Cohort 2 PCV20<br>Pneumococcal vaccine-naïve adult participants (18 to 49 years of age) receive a single dose of PCV20 on Day 1. | Biological: PCV20<br>* 0.5 mL injection suspension in prefilled syringe containing 2.2 μg of each PnPs antigen (1, 3, 4, 5, 6A, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, 33F) and 4.4 μg of PnPs antigen 6B.<br>* Other names: APEXXNAR™;|

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 consisted of pain/tenderness, redness/erythema, and swelling. | Up to 5 days postvaccination | 
| 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 consist of headache, muscle aches/myalgia, and tiredness/fatigue. | Up to 5 days postvaccination | 
| Percentage of participants with vaccine-related serious AE (SAE) | A vaccine-related SAE is any untoward medical consequence that 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 an other important medical event. | Up to 194 days postvaccination | 
| Serotype specific opsonophagocytic (OPA) geometric mean titers (GMTs) in Cohorts 1 and 2 for the 21 serotypes contained in V116 | The serotype specific OPA GMTs for the 21 serotypes contained in V116 will be determined using the multiplex opsonophagocytic assay (MOPA). | Day 30 postvaccination | 
| Percentage of participants with ≥4-fold rise from baseline in serotype specific OPAs in Cohort 1 for the 21 serotypes contained in V116 | The percentage of participants with ≥4-fold rise from baseline in serotype specific OPAs for the 21 serotypes contained in V116 will be determined. | Baseline and Day 30 postvaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with ≥4-fold rise in serotype specific cross-reactive OPA responses in Cohorts 1 and 2 | The percentage of participants with ≥4-fold rise from baseline in serotype specific cross-reactive OPAs will be determined. | Baseline and Day 30 postvaccination | 
| Serotype specific cross-reactive OPA GMTs in Cohorts 1 and 2 | The serotype specific OPA GMTs will be determined using MOPA. | Day 30 postvaccination | 
| Serotype specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) in Cohort 1 | The GMCs for serotype specific IgG antibodies will be determined using pneumococcal electrochemiluminescence (PnECL). | Day 30 postvaccination | 
| Geometric mean fold rise (GMFR) from baseline in serotype specific OPA GMTs in Cohort 1 | The GMFR from baseline in serotype specific OPA GMTs will be determined using MOPA. | Baseline and Day 30 postvaccination | 
| GMFR from baseline in serotype specific IgG GMCs in Cohort 1 | The GMFR in GMCs for serotype specific IgG antibodies will be determined using PnECL. | Baseline and Day 30 postvaccination | 
| Percentage of participants with ≥4-fold rise from baseline in serotype specific IgG GMCs in Cohort 1 | The percentage of participants with ≥4-fold rise from baseline in GMCs for serotype specific IgG antibodies will be determined using PnECL. | Baseline and Day 30 postvaccination | 
| Percentage of participants with ≥4-fold rise from baseline in serotype specific OPA GMTs in Cohort 1 | The percentage of participants with ≥4-fold rise from baseline in serotype specific OPAs will be determined. | Baseline and Day 30 postvaccination |