Phase II, Randomized, Observer-Blind, Single Center, Controlled Study of Two Doses of Various Formulations of WRAIR Live Attenuated Tetravalent Dengue Vaccine Compared to Placebo Control Administered on 0-6-Month Schedule to Healthy Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 86
- 试验地点
- 2
- 主要终点
- Percentage of Subjects Seropositive for Dengue Serotypes 1, 2, 3 and 4
研究概览
简要总结
This descriptive study will evaluate the safety and immunogenicity of 3 different formulations of the WRAIR dengue vaccine compared to a placebo.
详细描述
Subjects will be randomized into one of 4 groups. One group will receive a placebo vaccine and the others will receive one of 3 different dengue vaccine formations. Each subject will receive two doses six months apart. Study subjects who elect to participate in a mosquito transmissibility component of the study will undergo mosquito feedings during each of the two assigned follow-up visits after vaccine dose 1. All subjects will have 11 venipunctures during 11 visits (i.e., screening plus 10 study visits) over a period of nine months.
A third (booster) dose of post transfection F17 or F19 will be administered approximately 5 to 12 months after dose 2 to all subjects who received one of these formulation for their first two doses. Volunteers will return for a single visit 6 months after receiving their booster dose (long term follow-up)
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •A healthy male or female adult 18-45 years at the time of vaccination;
- •Free of obvious health problems as established by medical history and physical examination before entering into the study;
- •Written informed consent obtained from the subject;
- •Able to read the Subject Information Sheet and Consent Form;
- •Subjects who the investigator believes 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;
- •If the subject is female, she must be of non-childbearing potential, i.e. either 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; oral contraceptives or other equivalent hormonal contraception, e.g. progestin implantable, cutaneous hormonal patch or injectable contraceptives) for 30 days prior to vaccination, have a negative pregnancy test within 48 hours prior to vaccination and must agree to continue such precautions for 60 days after completion of the vaccination series.
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 drug abuse or alcohol consumption (more than 2 drinks per day);
- •History of allergic disease/reaction likely to be exacerbated by any component of the vaccine;
- •History of urticaria related to mosquito bites requiring medical attention;
- •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;
- •Subject seropositive for HBsAg, anti-HCV or anti-HIV;
- •Acute disease at the time of enrollment (acute disease is defined as the presence of a moderate or severe illness with or without fever);
- •(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., 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 days preceding the study vaccine (includes 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 days before each dose of the study vaccine and ending 30 days after;
- •A planned move to a location that will prohibit participating in the trial for 9 months after the initial vaccination;
- •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 90 days 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 days preceding the first dose or planned administration during the study period;
- •Any chronic systemic drug therapy to be continued during the study period (except for vitamin/mineral supplements, a single anti-hypertension medication or routine treatment for gastro-esophageal reflux).
结局指标
主要结局
Percentage of Subjects Seropositive for Dengue Serotypes 1, 2, 3 and 4
时间窗: Pre dose 1, 1 month post dose 1, 7 months post dose 2, Pre dose 3 and 1 month post dose 3
Serpositivity rates for DEN neut. antibodies -unprimed subjects (primary and booster ATP Cohort for immunogenicity) PRE = Pre dose PI(M1) = Post dose 1, month 1 PII(M7) = Post dose 2, month 7 PRE III = Pre dose 3 PIII(M1) = Post dose 3, month 1
N Antibody, Geometric Mean Titer(GMT) to Dengue Serotypes 1, 2, 3 and 4
时间窗: Pre dose 1, 1 month post dose 1, 7 months post dose 2, Pre dose 3 and 1 month post dose 3
GMTs for DEN neut. antibodies -unprimed subjects (primary and booster ATP Cohort for immunogenicity) PRE = Pre dose PI(M1) = Post dose 1, month 1 PII(M7) = Post dose 2, month 7 PRE III = Pre dose 3 PIII(M1) = Post dose 3, month 1
Occurrence of Any, and Grade 3 Solicited Adverse Events (AEs) Within 21 Days Follow-up After Dose 1 of Study Vaccine
时间窗: 21 days following 1st vaccination dose
Diary cards, digital thermometers, and small rulers were provided to subjects to record local and general solicited symptoms(pain, redness and swelling at the injection site, fatigue, headache, pain behind the eyes, abdominal pain, nausea, vomiting, muscle aches, joint aches, rash, photophobia and pruritis) and oral temperature taken daily for 21 days (days 0 through 20). The observations were to be recorded each evening and account for the previous 24 hours. If multiple temperature measurements were taken throughout the day, the maximum temperature was to be recorded.
次要结局
- Unsolicited Adverse Events Within 31 Days After Each Dose of Study Vaccine Dose(within 31 days of study vaccine)
- Neutralizing Antibody Sero-response to Each Dengue Serotype After Each Dose (Continued)(Days 0 to 270)
- Neutralizing Antibody Sero-response to Each Dengue Serotype After Each Dose(Days 0 to 270)
- Occurrence of Any, and Grade 3 Solicited Adverse Events (AEs) Within 21 Days Follow-up After Dose 2 of Study Vaccine;(within 21 days after vaccination)
- Occurrence of Serious Adverse Events (SAEs) Throughout the Entire Study Period.(Days 0 to 270)
- Occurrence of Abnormal Findings at Physical Examination After Each Vaccine Dose(throughout the 202 day study)
- Percentage of Subjects With Suspected and Confirmed Dengue Reported During the 31-day Post-vaccination Period (Total Vaccinated Cohort)(Days 0-30 post vaccination periods (total vaccinated cohort))
- Occurrence of Measurable Dengue Viremia at Specified Time Points Following Each Vaccine Dose.(Days 0 to 270)