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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,663
- 试验地点
- 112
- 主要终点
- Serotype Specific Opsonophagocytic (OPA) Geometric Mean Titers (GMTs) in Cohort 1 Only, for the Pneumococcal Serotypes Contained in V116 and PCV20
研究概览
简要总结
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.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Cohort 1 V116
Pneumococcal vaccine-naïve adult participants (≥50 years of age) receive a single dose of V116 on Day 1.
干预措施: V116 (Biological)
Cohort 2 V116
Pneumococcal vaccine-naïve adult participants (18 to 49 years of age) receive a single dose of V116 on Day 1.
干预措施: V116 (Biological)
Cohort 1 PCV20
Pneumococcal vaccine-naïve adult participants (≥50 years of age) receive a single dose of PCV20 on Day 1.
干预措施: PCV20 (Biological)
Cohort 2 PCV20
Pneumococcal vaccine-naïve adult participants (18 to 49 years of age) receive a single dose of PCV20 on Day 1.
干预措施: PCV20 (Biological)
结局指标
主要结局
Serotype Specific Opsonophagocytic (OPA) Geometric Mean Titers (GMTs) in Cohort 1 Only, for the Pneumococcal Serotypes Contained in V116 and PCV20
时间窗: Day 30 post-vaccination
The serotype specific OPA GMTs for the pneumococcal serotypes in cohort 1 of V116 and PCV20 only were determined using the multiplex opsonophagocytic assay (MOPA). GMT values were estimated from a constrained longitudinal data analysis; (cLDA) model. Per protocol, within group, confidence intervals (CIs) or any other measures of dispersion were not planned or determined. The 10 common pneumococcal serotypes in both V116 and PCV20 were as follows: 3, 6A, 7F, 8, 10A, 11A, 12F, 19A, 22F, and 33F. The 11 unique pneumococcal serotypes in V116 were as follows: 9N, 15A, 15C, 16F, 17F, 20A, 23A, 23B, 24F, 31, and 35B. Per protocol, Cohort 2 were not analyzed in this outcome measure.
Percentage of Participants With Solicited Injection-site Adverse Events (AEs)
时间窗: Up to 5 days post-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. Solicited injection-site AEs consist of the following: pain/tenderness, redness/erythema, and swelling.
Percentage of Participants With Vaccine-related Serious AE (SAE)
时间窗: Up to 194 days post-vaccination
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, which is determined by the investigator to be related to the vaccine.
Percentage of Participants With ≥4-fold Change From Baseline in Serotype Specific OPA Responses in Cohort 1 Only for the 11 Unique Pneumococcal Serotypes Contained in V116
时间窗: Baseline and Day 30 post-vaccination
The percentage of participants with ≥4-fold rise from baseline in serotype specific OPAs for the 11 unique pneumococcal serotypes contained in V116. Per protocol, within group CIs or any other measures of dispersion were not planned or determined. The 11 unique pneumococcal serotypes in V116 were as follows: 9N, 15A, 15C, 16F, 17F, 20A, 23A, 23B, 24F, 31, and 35B. Per protocol, Cohort 2 were not analyzed in this outcome measure.
Serotype Specific OPA GMTs in Participants 18-49 Years and Participants 50-64 Years for the Pneumococcal Serotypes Contained in V116
时间窗: Day 30 post-vaccination
The serotype specific OPA GMTs for the pneumococcal serotypes in participants 18-49 years and participants 50-64 years treated with V116 only were determined using the MOPA. GMT values were estimated from a cLDA model. Per protocol, within group CIs or any other measures of dispersion were not planned or determined. The 10 common pneumococcal serotypes in both V116 and PCV20 were as follows: 3, 6A, 7F, 8, 10A, 11A, 12F, 19A, 22F, and 33F. The 11 unique pneumococcal serotypes in V116 were as follows: 9N, 15A, 15C, 16F, 17F, 20A, 23A, 23B, 24F, 31, and 35B. Per protocol, participants treated with PCV20 were not analyzed in this outcome measure.
Percentage of Participants With Solicited Systemic AEs
时间窗: Up to 5 days post-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. Solicited systemic AEs consist of the following: fatigue (tiredness), headache, myalgia (muscle aches), and pyrexia (maximum temperature ≥ 100.4 °F/38.0 °C)
次要结局
- Percentage of Participants From Cohort 1 V116 With ≥4-fold Change in OPA Responses for Cross Reactive Pneumococcal Serotypes(Baseline and Day 30 post-vaccination)
- Geometric Mean Fold Change From Baseline in IgG Antibody GMCs in Cohort 1 for the Pneumococcal Serotypes Contained in V116 and PCV20(Baseline and Day 30 post-vaccination)
- Percentage of Participants With ≥4-fold Change From Baseline in IgG Antibody GMCs in Cohort 1 for the Pneumococcal Serotypes Contained in V116 and PCV20(Baseline and Day 30 post-vaccination)
- Serotype Specific OPA GMTs for Cross Reactive Pneumococcal Serotypes in Adults 50 to 64 Years of Age From Cohort 1 and Adults 18 to 49 Years of Age From Cohort 2(Day 30 post-vaccination)
- Percentage of Participants With ≥4-fold Change From Baseline in OPA GMTs in Cohort 1 for the Pneumococcal Serotypes Contained in V116 and PCV20(Baseline and Day 30 post-vaccination)
- Serotype Specific Immunoglobulin (IgG) Geometric Mean Concentrations (GMCs) in Cohort 1 Only, for the Pneumococcal Serotypes Contained in V116 and PCV20(Day 30 post-vaccination)
- Geometric Mean Fold Change From Baseline in OPA GMTs in Cohort 1 for the Pneumococcal Serotypes Contained in V116 and PCV20(Baseline and Day 30 post-vaccination)