A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by Administration of PNEUMOVAX™23 Six Months Later in Immunocompetent Adults Between 18 and 49 Years of Age at Increased Risk for Pneumococcal Disease (PNEU - DAY)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,515
- 试验地点
- 156
- 主要终点
- Percentage of Participants With a Vaccine-related Serious Adverse Event Following V114 or Prevnar 13™
研究概览
简要总结
This study is designed to 1) describe the safety, tolerability, and immunogenicity of V114 and Prevnar 13™ in pneumococcal vaccine-naïve adults at increased risk for pneumococcal disease and to 2) describe the safety, tolerability, and immunogenicity of PNEUMOVAX™23 when administered 6 months after receipt of either V114 or Prevnar 13™. Increased risk for pneumococcal disease is defined as 1) an underlying medical condition, 2) behavioral habits such as smoking or alcohol use, or 3) living in a community/environment with increased risk of disease transmission.
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 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Native American participant enrolled from any of the clinical sites of the Johns Hopkins Center for American Indian Health (CAIH) without any of the pre-specified risk conditions for pneumococcal disease listed below, OR Native American participant enrolled from any of the CAIH sites or participant from a site other than CAIH with ≥1 of the following risk conditions for pneumococcal disease:
- •Diabetes mellitus Type 1 or Type 2 and with hemoglobin A1c (HgA1c) <10%
- •Chronic liver disease with documented history of compensated cirrhosis (Child-Pugh Score A)
- •Confirmed diagnosis of Chronic Obstructive Pulmonary Disease (COPD) with spirometric Global Initiative for Chronic Obstructive Lung Disease Stage 1 to 3
- •Confirmed diagnosis of mild or moderate persistent asthma receiving guideline directed therapy
- •Confirmed diagnosis of chronic heart disease (New York Heart Association [NYHA] heart failure Class 1 to 3, receiving guideline-directed oral heart failure treatment) due to reduced or preserved ejection fraction or due to non-cyanotic congenital heart disease.
- •Current smoker
- •Female participant: not pregnant, not breastfeeding and 1) not of childbearing potential, or 2) of childbearing potential and agrees to practice contraception through 6 weeks after last administration of study vaccine.
排除标准
- •History of active hepatitis within the prior 3 months
- •History of diabetic ketoacidosis, or >1 episodes of severe, symptomatic hypoglycemia within the prior 3 months
- •Myocardial infarction, acute coronary syndrome, transient ischemic attack, and ischemic or hemorrhagic stroke within the prior 3 months
- •History of severe pulmonary hypertension or history of Eisenmenger syndrome
- •History of invasive pneumococcal disease (IPD) or known history of other culture-positive pneumococcal disease within the prior 3 years
- •Known hypersensitivity to any vaccine component, pneumococcal conjugate vaccine, or diphtheria toxoid-containing vaccine
- •Known or suspected impairment of immunological function (including human immunodeficiency virus (HIV) infection or autoimmune disease)
- •History of malignancy within the prior 5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
- •History of Stage 4 or 5 Chronic Kidney Disease or nephrotic syndrome
- •History of alcohol withdrawal or alcohol withdrawal seizure within the prior 12 months
- •History of coagulation disorder contraindicating intramuscular vaccination
- •History of hospitalization within the prior 3 months
- •Planned organ transplantation (heart, liver, lung, kidney, or pancreas) or other planned major surgery during the duration of this study.
- •Expected survival for less than 1 year according to the investigator's judgment.
- •Female participant: positive urine or serum pregnancy test
- •Prior administration of any pneumococcal vaccine
- •Received systemic corticosteroids (prednisone equivalent of ≥20 mg/day) for ≥14 consecutive days and has not completed within the prior 30 days
- •Received systemic corticosteroids exceeding physiologic replacement doses within 14 days before study vaccination
- •Receiving immunosuppressive or immunomodulatory therapy with a biological agent
- •Received any licensed, non-live vaccine within 14 days before receipt of study vaccine or is scheduled to receive any licensed, non-live vaccine within 30 days following receipt of study vaccine
- •Received any live vaccine within 30 days before receipt of any study vaccine or is scheduled to receive any live vaccine within 30 days following receipt of any study vaccine
- •Received a blood transfusion or blood products within the prior 6 months
- •Receiving chronic home oxygen therapy
- •Participated in another clinical study of an investigational product within the prior 2 months
- •Current user of recreational or illicit drugs or history of drug abuse or dependence
- •Diabetes mellitus with HgA1c ≥10%
- •Chronic liver disease with Child-Pugh Class B or C cirrhosis
- •Chronic lung disease with Chronic Obstructive Pulmonary Disease (COPD) GOLD Stage 4 or severe persistent asthma
- •Chronic heart disease with NYHA heart failure Class 4.
结局指标
主要结局
Percentage of Participants With a Vaccine-related Serious Adverse Event Following V114 or Prevnar 13™
时间窗: Up to Month 6 (before Vaccination 2)
A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. Relatedness of an SAE to the study vaccine was determined by the investigator. Following vaccination with V114 or Prevnar 13™, the percentage of serious adverse events of V114 compared with Prevnar 13™ was assessed. Estimated CIs are calculated based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Solicited Injection-site Adverse Events Following V114 or Prevnar 13™
时间窗: Up to 5 days after Vaccination 1
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Following Vaccination 1 with either V114 or Prevnar 13™, the percentage of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs assessed were redness/erythema, swelling, and tenderness/pain. Estimated confidence intervals (CIs) are calculated based on the exact binomial method proposed by Clopper and Pearson.
Percentage of Participants With Solicited Systemic Adverse Events Following V114 or Prevnar 13™
时间窗: Up to 14 days after Vaccination 1
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Following vaccination with V114 or Prevnar 13™, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. Estimated CIs are calculated based on the exact binomial method proposed by Clopper and Pearson.
Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity Day 30 Following V114 or Prevnar 13™
时间窗: Day 30
The geometric mean titer (GMT) of serotype-specific opsonophagocytic activity (OPA) for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a multiplex opsonophagocytic assay. The within-group 95% CIs are obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.
次要结局
- Geometric Mean Concentration of Serotype-specific Immunoglobulin G at Day 30(Day 30)
- Percentage of Participants With Solicited Injection-site Adverse Events Following PNEUMOVAX™23(Up to 5 days after Vaccination 2 (Month 6))
- Percentage of Participants With Solicited Systemic Adverse Events Following PNEUMOVAX™23(Up to 14 days after Vaccination 2 (Month 6))
- Percentage of Participants With a Vaccine-related Serious Adverse Event Following PNEUMOVAX™23(From Month 6 (before Vaccination 2) to Month 7)
- Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Day 1 to Day 30(Day 1 (Baseline) and Day 30)
- Geometric Mean Titer of Serotype-specific OPA at Month 7(Month 7)
- GMFR in Serotype-specific IgG Month 6 to Month 7(Month 6 (Baseline before Vaccination 2) and Month 7)
- Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Month 6 to Month 7(Month 6 (Baseline before Vaccination 2) and Month 7)
- Geometric Mean Fold Rise in Serotype-specific OPA Day 1 to Day 30(Day 1 (Baseline) and Day 30)
- GMFR in Serotype-specific IgG Day 1 to Month 7(Day 1 (Baseline) and Month 7)
- GMFR in Serotype-specific IgG Day 1 to Day 30(Day 1 (Baseline) and Day 30)
- Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Day 1 to Day 30(Day 1 (Baseline) and Day 30)
- Geometric Mean Concentration of Serotype-specific IgG at Month 7(Month 7)
- Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Day 1 to Month 7(Day 1 (Baseline) and Month 7)
- Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Day 1 to Month 7(Day 1 (Baseline) and Month 7)
- GMFR in Serotype-specific OPA Day 1 to Month 7(Day 1 (Baseline) and Month 7)
- GMFR in Serotype-specific OPA Month 6 to Month 7(Month 6 (Baseline before Vaccination 2) and Month 7)
- Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Month 6 to Month 7(Month 6 (Baseline before Vaccination 2) and Month 7)