Safety and Immunogenicity of V116 in Adults With Increased Risk for Pneumococcal Disease (V116-008)

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the safety and tolerability of the pneumococcal 21 valent conjugate vaccine (V116), and to evaluate the serotype-specific opsonophagocytic activity (OPA) post-vaccination with V116 and PCV15 (a pneumococcal conjugate vaccine that includes 15 serotypes) + PPSV23 (comprised of the polysaccharides from 23 of the serotypes causing disease in adults) post-vaccination. within each vaccination group separately.

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 18 to 64 Years of Age With Increased Risk for Pneumococcal Disease

Conditions
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Pneumococcal Infection

Intervention / Treatment
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* Biological: V116
* Drug: Placebo for PCV15 + PPSV23
* Biological: PCV15
* Biological: PPSV23


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has documented result(s) of ≥1 of the following risk conditions for pneumococcal disease: diabetes mellitus, receiving treatment with ≥1 approved antidiabetic medication, with all Hemoglobin A1c (HbA1c) measurements ≤9% within 6 months before first study vaccination; compensated chronic liver disease; diagnosis of chronic obstructive pulmonary disease (COPD) managed per local guidelines; diagnosis of mild or moderate persistent asthma managed per local guidelines; confirmed diagnosis of chronic heart disease managed per local guidelines; confirmed diagnosis of chronic kidney disease (>3 months duration). Is receiving stable medical management for the listed risk conditions for ≥3 months with no anticipated major change in treatment expected for the duration of the study and with ≤1 hospitalization directly related to the risk condition. Female Is not a participant of childbearing potential (POCBP); or if a POCBP Uses an acceptable contraceptive method or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis); their medical history, menstrual history, and recent sexual activity has been reviewed by the investigator. Exclusion Criteria: Has a history of active hepatitis. Has a history of diabetic ketoacidosis or 2 or more episodes of severe, symptomatic hypoglycemia within 3 months before first study vaccination (Day 1). Has a history of myocardial infarction, acute coronary syndrome, transient ischemic attack, or ischemic or hemorrhagic stroke within 3 months before first study vaccination (Day 1). Has a history of severe pulmonary hypertension with World Health Organization (WHO) functional class ≥3 or history of Eisenmenger syndrome Has a history of autoimmune related chronic kidney disease, chronic kidney failure, a reversible cause of kidney disease, nephrotic syndrome, or any ineligible Kidney Disease: Improving Global Outcomes (KDIGO)-recommended stage of glomerular filtration rate (GFR) and Albuminuria 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 before first study vaccination (Day 1). Has a known hypersensitivity to any component of V116, PCV15, or PPSV23, including diphtheria toxoid. Has a known or suspected impairment of immunological function including, but not limited to, congenital or acquired immunodeficiency, documented human immunodeficiency virus (HIV) infection, functional or anatomic asplenia, or autoimmune disease. Has a coagulation disorder contraindicating intramuscular (IM) vaccination. Had a recent febrile illness or received antibiotic therapy for any acute illness occurring within 72 hours before receipt of any study vaccine. Has a known malignancy that is progressing or has required active treatment <3 years before randomization. Has planned organ transplantation (heart, liver, lung, kidney, or pancreas) or other planned major surgical procedure during the duration of this study. Has expected survival for <1 year. Has received any prior pneumococcal vaccine or is expected to receive any pneumococcal vaccine during the study outside the protocol. Has 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 at Visit 2 (Day 1). Is currently receiving systemic 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 any 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 (including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) live virus vaccines) ≤30 days before receipt of any study vaccine or is scheduled to receive any live virus vaccine ≤30 days after receipt of any study vaccine Has received a blood transfusion or blood products, including immunoglobulin ≤6 months before receipt of any study vaccine or is scheduled to receive a blood transfusion or blood product ≤30 days after receipt of any study vaccine. Is receiving chronic home oxygen therapy.

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
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V116<br>Participants will receive a single intramuscular (IM) dose of V116 on Day 1, and single IM dose of placebo for PCV15 + PPSV23 on Week 8 | 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;Drug: Placebo for PCV15 + PPSV23<br>* Saline in each 0.5 mL sterile solution<br>|
| Active Comparator: PCV15 + PPSV23<br>Participants will receive a single IM dose of PCV15 on Day 1, and a single IM dose of PPSV23 on Week 8. | Biological: PCV15<br>* Pneumococcal 15-valent conjugate vaccine with 2 μg of each of the following PnPs antigen: 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F; and 4 μg of PnPs antigen 6B in each 0.5 mL sterile suspension<br>* Other names: VAXNEUVANCE™;Biological: PPSV23<br>* Pneumococcal 23-valent polyvalent 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 |
| --- | --- | --- |
| Participants with solicited injection-site adverse events (AEs) from Day 1 through Day 5 post-vaccination | Percentage of participants with solicited injection-site AEs from Day 1 through Day 5 post-vaccination | Up to Day 5 | 
| Participants with solicited systemic AEs from Day 1 through Day 5 post-vaccination | Percentage of participants with solicited systemic AEs from Day 1 through Day 5 post-vaccination | Up to Day 5 | 
| Participants with vaccine-related serious adverse events (SAEs) from Day 1 through the duration of participation in the study | Percentage of participants with vaccine-related SAEs from Day 1 through the duration of participation in the study | Up to Month 6 | 
| Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) post-vaccination | Serotype-specific OPA GMTs post-vaccination with V116 (30 days post-vaccination [Day 30]) or PCV15 + PPSV23 (30 days post-vaccination with the final dose in the regimen [Week 12]) | Up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) post-vaccination | Serotype-specific IgG GMCs post-vaccination with V116 (Day 30) and PCV15 + PPSV23 (Week 12) | Up to Week 12 | 
| Serotype-specific geometric mean fold rises (GMFRs) from baseline to post-vaccination with V116 and PCV15 + PPSV2 for OPA responses | Serotype-specific GMFRs from baseline (Day 1) to post-vaccination with V116 (Day 30) and from baseline (Day 1) to post=vaccination with PCV15 + PPSV2 (Week 12) for OPA responses | Baseline and up to Week 12 | 
| Serotype-specific GMFRs from baseline to post-vaccination with V116 and PCV15 + PPSV2 for Immunoglobulin G (IgG) responses | Serotype-specific GMFRs from baseline (Day 1) to post-vaccination with V116 (Day 30) and from baseline (Day 1) to post-vaccination with PCV15 + PPSV23 (Week 12) for IgG responses | Baseline and up to Week 12 | 
| Serotype-specific percentage of participants with a ≥4-fold rise from baseline to post-vaccination with V116 and PCV15 + PPSV2 for OPA responses | Serotype-specific percentage of participants with a ≥4-fold rise from baseline (Day 1) to post-vaccination with V116 (Day 30) and from baseline (Day 1) to post-vaccination with PCV15 + PPSV2 (Week 12) for OPA responses | Baseline and up to Week 12 | 
| Serotype-specific percentage of participants with a ≥4-fold rise from baseline to post-vaccination with V116 and PCV15 + PPS for IgG responsesV2 | Serotype-specific proportion of participants with a ≥4-fold rise from baseline (Day 1) to post-vaccination with V116 (Day 30) and from baseline (Day 1) to post-vaccination with PCV15 + PPSV2 (Week 12) for IgG responses | Baseline and up to Week 12 |