Randomized, Double-blind, Placebo Controlled Phase II Trial of the Safety, Tolerability and Immunogenicity of Lyophilized ChimeriVax-WN02 West Nile Vaccine in Healthy Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 208
- 试验地点
- 10
- 主要终点
- Number of Participants With Fourfold or Greater Post-vaccination Titers (Seroconversion).
研究概览
简要总结
The purpose of this study is to determine whether a single subcutaneous injection of ChimeriVax-WN02 vaccine is well tolerated, safe and induces protective antibodies against West Nile Disease. The study is divided into two parts; in the first part, a comparison of 3 dose levels of the vaccine will be made, with an inactive control. In the second part, the optimum dose level chosen after the first part will be given to older volunteers.
详细描述
West Nile Disease has been carried across the United States by migrating birds since it was first identified in New York city in 1999. It is transmitted by mosquitoes from birds to humans and can cause severe disease in some individuals. There is no specific treatment for West Nile Disease. The target population for a West Nile vaccine is older people, as they are more susceptible to severe disease. This trial includes a dose-finding part with a placebo control in young healthy adults, followed by a placebo-controlled examination of the chosen dose in older healthy adults.
Outcome measures include a comparison of adverse events between active treatment and placebo, a comparison of antibody and viremia measurements between dose levels and across age groups for the dose chosen for Part 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Healthy adult aged 18 to 40 years.
- •Women of child-bearing potential should be using hormonal contraception.
- •Subject had to be available for the study duration, including all planned follow-up visits.
排除标准
- •Previous vaccination against yellow fever or Japanese encephalitis
- •History of flavivirus infection
- •Any abnormalities of immune system, or using drugs that affect the immune system.
- •History of anaphylaxis to foods, bee stings, vaccines or drugs.
- •Receipt of blood or blood products within the preceding 6 months.
- •Receipt of any vaccine in the preceding 30 days
- •Seropositive to hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) or Human immunodeficiency virus (HIV)
- •Lactation or intended pregnancy in female subjects
- •Previous or current military service with overseas deployment
- •Travel to Mexico or other flavivirus endemic areas in the tropics for periods of four weeks or more in the previous ten years.
- •Inclusion Criteria: Part 2
- •Aged ≥ 41 years.
- •Subjects had to be in general good health.
- •Unimpaired cognitive performance as assessed by clock drawing test score
- •Subject had to be available for all required study visits, including all planned follow-up visits.
- •Women of child-bearing potential should be using hormonal contraception.
- •Exclusion Criteria: Part 2
- •Clinically significant abnormalities on the Screening 12-lead electrocardiogram (ECG).
- •An acute or chronic medical condition that, in the opinion of the Investigator, would render vaccination unsafe or would interfere with the evaluation of responses. These conditions included, but were not limited to:
- •History of renal impairment
- •History of significant liver disease or hepatic impairment
- •History of diabetes mellitus (except controlled with diet)
- •An arteriosclerotic event during the 6 months prior to enrollment (including but not limited to myocardial infarction or unstable angina, peripheral bypass surgery for revascularization of an extremity, and transient ischemic attack or stroke)
- •Signs of congestive heart failure at the time of enrollment
- •Subjects with 3 or more of the following:
- •Age over 50 years
- •Hypercholesterolemia, or significantly abnormal lipid profile, based on medical history
- •Any prior history of cardiovascular disease
- •Significant family history of cardiovascular disease in any immediate relative
- •History of significant collagen vascular disease.
- •The unexplained presence of any of the following findings:
- •Any significant episodes of confusion, memory loss, language impairment, other cognitive impairment, or other abnormal behavior if relatively abrupt in onset
- •Clinically significant depression
- •Sudden visual impairment (e.g., loss of vision, double vision)
- •Slurred or abnormal speech
- •Sudden onset of vertigo
- •Focal weakness in any extremity
- •Focal sensory loss in any extremity
- •Impaired balance
- •Impaired gait.
- •Subjects with any diagnosis of dementia or associated concomitant medications (e.g., Aricept) used for treating dementia.
- •Subjects with active or a history of neurologic disease or injury, including, but not limited to: Parkinson's, Guillain Barre, epilepsy (except febrile seizures in youth not treated with medication), cerebrovascular accident, head trauma, or any other neurologic condition thought to impact the integrity of the blood-brain barrier.
- •Subjects taking warfarin, heparin, or with known bleeding disorders.
- •Relative or employee of the study site staff, CRO, or Sponsor participating in this trial.
- •A history of vaccination against yellow fever (YF) or Japanese encephalitis. Previous vaccination was determined by history (interview of subject) and/or by reviewing the subject's vaccination card or other official documentation.
- •History of flavivirus infection (e.g. West Nile [WN], Systemic Lupus Erythematosus [SLE], Japanese encephalitis, dengue fever).
- •History of thymoma, thymic surgery (removal), or myasthenia gravis.
- •Known or suspected immunodeficiency disorder, including leukemia, lymphoma, generalized malignancy, or treatment with immunosuppressive medications, including corticosteroids, alkylating agents, anti-metabolites, or radiation therapy. Low dose steroids (≤ 10 mg prednisone or equivalent, topical or intra articular/bursal/tendon/epidural injections of corticosteroids) did not constitute a reason for exclusion.
- •History of residence in or travel to Mexico or flavivirus endemic areas in the tropics (India, southeast Asia, Central America, Caribbean, or South America) for periods of 4 weeks or more within the last 10 years.
- •Subjects with clinically significant screening laboratory abnormalities and/or those having any of the following:
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结局指标
主要结局
Number of Participants With Fourfold or Greater Post-vaccination Titers (Seroconversion).
时间窗: Day 28 post-vaccination
Seroconversion was defined as a fourfold or greater rise in titer between pre- and post-immunization samples
Number of Viremic Participants Post-vaccination
时间窗: Day 21 post-vaccination
Viremic = detectable level of ≥ 10 plaque-forming units (PFU)/mL
Treatment-emergent Adverse Events Reported As Related to Study Treatment in at Least 5% of Participants in Any Active Treatment Group Post-vaccination.
时间窗: Days 0 to 28 post-vaccination
次要结局
- Geometric Mean Titers of Neutralizing Antibody Titers Pre- and Post-vaccination.(Days 0, 14, and 28 post-vaccination)