Phase II, Randomized, Double-blind, Placebo-controlled Study of Two Doses of WRAIR Live Attenuated Tetravalent Dengue Vaccine Formulations, Administered Six Months Apart, to Healthy Adults and Children
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 636
- 试验地点
- 20
- 主要终点
- Safety: Incidence of All and Grade 3 Solicited Local Symptoms
研究概览
简要总结
The purpose of this study is to evaluate the safety and effectiveness of two different formulations of an investigational dengue vaccine (T-DEN) against a placebo vaccine when two doses are given six months apart to adults and children.
详细描述
In this study, children and adults at multiple sites in Puerto Rico will be randomly allocated to receive one of two T-DEN formulations or placebo. Subjects will be stratified by age group (a specific number of subjects in each of 4 age groups [12 months to 50 years of age] will be enrolled). The study includes 6 scheduled visits and 4 scheduled venipunctures. Safety follow-up for dengue may require unscheduled visits and venipunctures.> Multiple DEN virus serotypes are endemic in Puerto Rico and all residents are considered to be at risk for dengue. The results of this phase II study will provide a basis for identifying the vaccine formulations which elicit neutralizing antibodies to all four dengue virus serotypes in a high proportion of vaccine recipients. The most immunogenic and well tolerated candidate formulation identified in this study will be considered for advancement to phase III development.>
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 12 Months 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects who the investigator believes that they and/or their parents/guardians can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits) should be enrolled in the study.>
- •A healthy male or non-pregnant female between 12 months (mths) and 50 years (yrs) of age at the time of the first vaccination;>
- •Free of obvious health problems as established by medical history and physical examination before entering into the study;>
- •For children: 23mths of age, full compliance with the United States Advisory Committee on Immunization Practices (U.S. ACIP) recommended childhood immunization schedule;>
- •Written informed consent obtained from the subject or a parent/guardian and assent for subjects 7-20 yrs of age;>
- •If the subject is female, she must be of non-childbearing potential, i.e. either pre-menarcheal, surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (i.e. intrauterine contraceptive device; condom and spermicide combination, oral contraceptives or other equivalent hormonal contraception, e.g. progestin implantable, cutaneous hormonal patch or injectable contraceptives) for 30 days (dys) prior to vaccination, have a negative pregnancy test within 48 hrs prior to vaccination and must agree to continue such precautions for 60 dys after completion of the vaccination series. Any child who begins menarche during the study period must follow the same precautions listed above, from menarche until 60 dys after the second vaccine dose.>
排除标准
- •Pregnant or lactating female;>
- •Female planning to become pregnant or planning to discontinue abstinence or contraceptive precautions;>
- •History of any neurological or behavioral disorder or seizures, with the exception of a single febrile seizure in childhood; >
- •History of allergic disease/reaction likely to be exacerbated by any component of the vaccine;>
- •Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal, hematologic or endocrine functional defect, as determined by physical examination or laboratory tests;>
- •Any confirmed or suspected immunosuppressive or immunodeficient condition;>
- •Acute disease at the time of enrollment (acute disease is defined as the presence of a moderate or severe illness with or without fever); note that vaccine can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., equivalent to an oral temperature <37.5°C/<99.5°F.>
- •Chronic hepatomegaly, right upper quadrant abdominal pain or tenderness;>
- •Chronic splenomegaly, left upper quadrant abdominal pain or tenderness;>
- •Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 dys preceding the first dose of study vaccine/placebo or planned use during the study period;>
- •Planned administration of a vaccine not foreseen by the study protocol during the period starting from 30 dys before each dose of the study vaccine and ending 30 dys after; with the exception of standard infant and children "inactivated" vaccines or the inactivated influenza vaccine administered to adults or children; >
- •A planned move to a location that will prohibit participating in the trial for the 12 mth duration;>
- •Chronic administration (defined as more than 14 dys) of immunosuppressants or other immune-modifying drugs within 90 dys preceding the first dose or planned administration during the study period. For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed;>
- •Administration of immunoglobulins and/or blood products within 90 dys preceding the first dose or planned administration during the study period;>
- •Hypertension;>
- •Chest pain, palpitations, dizziness, shortness of breath unrelated to asthma, arrhythmias or friction rubs;>
- •Any chronic systemic drug therapy to be continued during the study period (except for vitamin/mineral supplements, routine treatment for gastro-esophageal reflux);>
- •Potential adult volunteers, or parents of potential child volunteers, who do not have easy access to a fixed or mobile telephone;>
- •History of chronic alcohol consumption and/or drug abuse.
结局指标
主要结局
Safety: Incidence of All and Grade 3 Solicited Local Symptoms
时间窗: Within 21 days (days 0-20) f/up period after each vaccine dose
Incidence of all and grade 3 (prevents normal, everyday activities) solicited local and general symptoms within the 21-day follow-up period (Total vaccinated cohort)
Safety: Occurrence of Serious Adverse Events (SAEs)
时间窗: 6 months + 30 day follow-up period after last vaccine dose
Summary of SAEs, 6 months + 30 day follow-up period after last vaccine dose
Safety: Summary of Unsolicited Adverse Events Within the 31-day Post-vaccination Period
时间窗: Within the 31-day (days 0-30) follow-up period after each vaccine dose
Summary of unsolicited Adverse Events within the 31-day post-vaccination period by age group (total vaccinated cohort)
次要结局
- Vaccine Response to DEN Antibody at Post Dose 1, Month 3(at month 3, post dose 1)
- Percent of Subjects With Neut. Antibody Titer Above the Assay Cut-off to All Dengue Serotypes(Pre-vaccination, at post dose 1, months 3 and 6 and post dose 2, month 7)
- Percent of Subjects With Neut. Sero-response to Each DEN Serotype(Pre-accination, at post dose 1, months 3 and 6 and post dose 2, month 7)
- Vaccine Response to DEN Antibody at Post Dose 2, Month 7(at month 7, post dose 2)
- Incidence of Suspected and Laboratory Confirmed Dengue(31-day (days 0-30) post-vaccination period and after 31-day period)
- GMTs for Antibody Titer Above the Assay Cut Off to Each DEN Serotype for Unprimed and Primed Subjects(at month 7 (one month post dose 2))