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.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 518
- 试验地点
- 44
- 主要终点
- Percentage of Participants With Solicited Injection-site Adverse Events (AEs) From Day 1 Through Day 5 Post-vaccination
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
V116 + Placebo
Participants administered a single intramuscular (IM) dose of V116 on Day 1, and single IM dose of placebo on Week 8.
干预措施: V116 (Biological)
V116 + Placebo
Participants administered a single intramuscular (IM) dose of V116 on Day 1, and single IM dose of placebo on Week 8.
干预措施: Placebo (Biological)
PCV15 + PPSV23
Participants administered a single IM dose of PCV15 on Day 1, and a single IM dose of PPSV23 on Week 8.
干预措施: PCV15 (Biological)
PCV15 + PPSV23
Participants administered a single IM dose of PCV15 on Day 1, and a single IM dose of PPSV23 on Week 8.
干预措施: PPSV23 (Biological)
结局指标
主要结局
Percentage of Participants With Solicited Injection-site Adverse Events (AEs) From Day 1 Through Day 5 Post-vaccination
时间窗: Up to 5 days following each vaccination
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. The percentage of participants with solicited injection-site AEs was assessed following any vaccination. Solicited injection-site AEs consist of the following: pain/tenderness, redness/erythema, and swelling.
Participants With Solicited Systemic AEs From Day 1 Through Day 5 Post-vaccination
时间窗: Up to 5 days following each vaccination
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. The percentage of participants with solicited systemic AEs was assessed following any vaccination. Solicited systemic AEs consist of the following: fatigue (tiredness), headache, myalgia (muscle aches), and pyrexia (maximum temperature \>= 100.4 °F/38.0 °C).
Participants With Vaccine-related Serious Adverse Events (SAEs) From Day 1 Through The Duration of Participation in The Study
时间窗: Up to 194 days following Visit 2 (Day 1)
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 another important medical event, which is determined by the investigator to be related to the vaccine. The percentage of participants with SAEs was assessed following any vaccination.
Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for Pneumococcal Serotypes Contained in V116
时间窗: 30 days following V116 [Day 30] for the V116 + Placebo group and 30 days following PPSV23 [Week 12] for the PCV15 + PPSV23 group.
The serotype specific OPA GMTs for the pneumococcal serotypes were determined using the multiplex opsonophagocytic assay (MOPA). The point estimate was calculated by exponentiating the estimates of the mean of the natural log values and within-group 95% CIs were obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution. The 13 common pneumococcal serotypes in both V116 and PCV15 + PPSV23 were as follows: 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 17F, 19A, 20A, 22F, and 33F. The 8 unique pneumococcal serotypes in V116 were as follows: 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B.
次要结局
- Serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for Pneumococcal Serotypes Contained in V116(30 days following V116 [Day 30] for the V116 + Placebo group and 30 days following PPSV23 [Week 12] for the PCV15 + PPSV23 group.)
- Serotype-specific Geometric Mean Fold Rises (GMFRs) for OPA Responses From Baseline to Post-vaccination With V116 and PCV15 + PPSV23(Baseline (Day 1) and postvaccination (30 days following V116 [Day 30] for the V116 + Placebo group and 30 days following PPSV23 [Week 12] for the PCV15 + PPSV23 group))
- Serotype-specific GMFRs for IgG Responses From Baseline to Post-vaccination With V116 and PCV15 + PPSV23(Baseline (Day 1) and postvaccination (30 days following V116 [Day 30] for the V116 + Placebo group and 30 days following PPSV23 [Week 12] for the PCV15 + PPSV23 group))
- Percentage of Participants With ≥4-fold Change From Baseline to Post-vaccination With V116 and PCV15 + PPSV23 in Serotype Specific OPA Responses for Pneumococcal Serotypes Contained in V116(Baseline (Day 1) and postvaccination (30 days following V116 [Day 30] for the V116 + Placebo group and 30 days following PPSV23 [Week 12] for the PCV15 + PPSV23 group))
- Percentage of Participants With ≥4-fold Change From Baseline to Post-Vaccination With V116 and PCV15 + PPSV23 in Serotype Specific IgG Responses for Pneumococcal Serotypes Contained in V116(Baseline (Day 1) and postvaccination (30 days following V116 [Day 30] for the V116 + Placebo group and 30 days following PPSV23 [Week 12] for the PCV15 + PPSV23 group))