Safety and Immunogenicity of V116 in Vaccine-naïve Japanese Older Adults (V116-009, STRIDE-9)

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 in pneumococcal vaccine-naïve Japanese adults 65 years of age and older. The polyvalent (23-valent) pneumococcal vaccine, PPSV23, is the active comparator. In addition to studying safety/tolerability, it is hypothesized that, at 30 days postvaccination, the immunogenicity of V116 is noninferior to PPSV23 for the 12 common serotypes in V116 and PPSV23 and the cross-reactive serotype 15B in V116, and that the immunogenicity of V116 is superior to PPSV23 for the unique serotype 15C in V116. It is also hypothesized that V116 is superior to PPSV23 in the percentage of participants with ≥4-fold rise from baseline in the 8 unique V116 serotypes (except for 15C), as measured by serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs).

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 Japanese Adults 65 Years of Age or Older

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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Inclusion Criteria: Is Japanese For females, is not pregnant or breastfeeding and is either not a participant of childbearing potential (POCBP) or is a POCBP and uses acceptable contraception/abstinence; has a negative highly sensitive pregnancy test (urine or serum) within 24 (urine) or 72 (serum) hours before the first dose of study intervention; and has medical, menstrual, and recent sexual activity history reviewed by the investigator to decrease the chance of inclusion 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 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 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 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: 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V116 Treatment<br>Participants receive a single intramuscular (IM) injection of V116 on Day 1. | Biological: V116<br>* Sterile 0.5 mL solution in prefilled syringe containing 4 μg of each pneumococcal polysaccharide (PnPs) antigen 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B.<br>* Other names: Pneumococcal 21-valent Conjugate Vaccine;|
| Active Comparator: PPSV23 Treatment<br>Participants receive a single IM injection of PPSV23 on Day 1. | Biological: PPSV23<br>* Sterile 0.5 mL solution in prefilled syringe containing 25 μg of each 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.<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 consist 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 muscle aches all over body/myalgia, headache, and tiredness/fatigue. | Up to 5 days postvaccination | 
| Percentage of participants with vaccine-related serious AEs (SAEs) | An SAE is any untoward medical occurrence 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. SAEs that were reported to be at least possibly related by the investigator to study vaccination will be summarized. | Up to 30 days postvaccination | 
| Serotype-specific opsonophagocytic (OPA) geometric mean titers (GMTs) [common serotypes] | The serotype-specific OPA GMTs for the 12 common serotypes contained in V116 and PPSV23, the cross-reactive serotype 15B in V116, and the unique serotype 15C 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 (unique to V116) | The percentage of participants with ≥4-fold rise from baseline in serotype-specific OPAs for the 8 unique serotypes contained in V116 (except for 15C) will be determined. | Baseline (Day 1) and Day 30 postvaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serotype-specific OPA GMTs (unique serotypes) | The serotype-specific OPA GMTs for the 8 unique serotypes contained in V116 (except for serotype 15C) and the cross-reactive serotype 6C in V116 will be determined using MOPA. | Day 30 postvaccination | 
| Serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) | The GMCs for serotype-specific IgG antibodies will be determined using pneumococcal electrochemiluminescence (PnECL). | Day 30 postvaccination | 
| Percentage of participants with ≥4-fold rise from baseline in serotype-specific OPA GMTs (all serotypes) | The percentage of participants with ≥4-fold rise from baseline in serotype-specific OPA GMTs will be determined with MOPA. | Baseline (Day 1) and Day 30 postvaccination | 
| Percentage of participants with ≥4-fold rise from baseline in serotype-specific IgG GMCs (all serotypes) | The percentage of participants with ≥4-fold rise from baseline in serotype-specific IgG GMCs will be determined with PnECL. | Baseline (Day 1) and Day 30 postvaccination | 
| Serotype-specific geometric mean fold rise (GMFR) in OPA GMTs | The GMFR from baseline in serotype-specific OPA GMTs will be determined using MOPA. | Baseline (Day 1) and Day 30 postvaccination | 
| Serotype-specific GMFR in IgG GMCs | The GMFR from baseline in GMCs for serotype-specific IgG antibodies will be determined using PnECL. | Baseline (Day 1) and Day 30 postvaccination |