A Phase I, Randomized, Placebo-Controlled, Observer-blind, Two-dose (0-28 Day Schedule) Primary Vaccination Study of Walter Reed Army Institute of Research (WRAIR) Tetravalent Dengue Virus Purified Inactivated Vaccine (TDENV-PIV) in Healthy Adults in a Non-Endemic Region
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Number of Subjects With Adverse Events Within the 28 Day Follow-up
研究概览
简要总结
The study is designed to afford a safety and immunogenicity assessment of three Tetravalent Dengue Virus-Purified Inactivated Vaccine(TDENV-PIV) vaccine candidates.
详细描述
The study is designed to afford a safety and immunogenicity assessment of three Tetravalent Dengue Virus-Purified Inactivated Vaccine(TDENV-PIV) vaccine candidates, each formulated with a different adjuvant: either aluminum hydroxide, AS01E or AS03B (adjuvants used in Glaxo Smith Kline (GSK) Biologicals' hepatitis B candidate vaccine, malaria candidate vaccine and pandemic flu vaccine, respectively). Each vaccine candidate will contain 1 µg of purified virus antigen per each of the four DENV types. Additionally, the study will evaluate an alum adjuvanted TDENV-PIV vaccine candidate containing 4 µg of purified virus antigen per each of the four DENV types. The control group will receive a saline placebo. All experimental vaccinations will be administered according to a 2-dose schedule, 28 days apart.
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 39 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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, etc.)
- •A male or female between 18 and 39 years of age (inclusive) at the time of consent
- •Written informed consent obtained from the subject
- •Healthy subjects as established by medical history and clinical examination before entering into the study
- •Female subjects of non-childbearing potential (non-childbearing potential is defined as having either a current tubal ligation at least three months prior to enrollment, hysterectomy, ovariectomy, or is post-menopause). See Definition of Terms for adequate contraception.
- •Female subjects of childbearing potential may be enrolled in the study, if the subject has:
- •Practiced adequate contraception for 30 days prior to vaccination, and
- •A negative urine pregnancy test on the day of vaccination, and
- •Agreed to continue adequate contraception until two months after completion of the vaccination series
排除标准
- •Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines/placebo during the period starting 30 days preceding the first dose of study vaccine/placebo and/or planned use during the study period
- •Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 180 days prior to the first vaccine/placebo dose (for corticosteroids, this will mean prednisone ≥ 20 mg/day or equivalent; inhaled and topical steroids are allowed)
- •Planned administration or administration of a vaccine/product not foreseen by the study protocol during the period starting 30 days prior to the first dose of vaccine/placebo until after the visit at Day 56 (if influenza activity warrants vaccination of healthy young adults, influenza vaccination will be encouraged and will not lead to study exclusion)
- •Planned administration of any flavivirus vaccine for the entire study duration
- •Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
- •Family history of congenital or hereditary immunodeficiency
- •History of, or current auto-immune disease
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine/placebo or related to a study procedure
- •Major congenital defects or serious chronic illness
- •History of any neurological disorders or seizures
- •Acute disease and/or fever (≥37.5°C/99.5°F oral body temperature) at the time of enrollment (a subject with a minor illness, i.e., mild diarrhea, mild upper respiratory infection, etc., without fever, may be enrolled at the discretion of the investigator)
- •Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality,as determined by physical examination or laboratory screening tests
- •Administration of immunoglobulins and/or any blood products during the period starting 90 days preceding the first dose of study vaccine/placebo or planned administration during the study period
- •History of chronic alcohol consumption and/or drug abuse
- •Pregnant or lactating female or female planning to become pregnant or planning to discontinue contraceptive precautions
- •A planned move to a location that will prohibit participating in the trial until study end for the participant
- •Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.
- •Subject seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)
- •Safety laboratory test results that are outside the acceptable values at screening. The following values are not acceptable:
- •>110% upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, creatinine, serum urea nitrogen (SUN) and bilirubin (total and direct)
- •<100% lower limit of normal (LLN) or > 120% ULN for hemoglobin, hematocrit and platelet count
- •<75% LLN or >110% ULN for total white blood cell count (WBC) Note that all screening laboratory results must be either within normal limits (WNL) or no more than Grade l not clinically significant (NCS)
- •(LLN=lower limit of normal; ULN= upper limit of normal, WNL= within normal limits, NCS= not clinically significant)
研究组 & 干预措施
TDENV-PIV alum4
4 µg TDENV-PIV with Alum adjuvant; 0.5 mL intramuscular injection at 0 and 28 days
干预措施: 4 µg TDENV-PIV with Alum adjuvant (Biological)
TDENV-PIV AS01E1
1 µg TDENV-PIV with AS01E1 adjuvant; 0.5 mL intramuscular injection at 0 and 28 days
干预措施: 1 µg TDENV-PIV with AS01E1 adjuvant (Biological)
TDENV-PIV AS03B1
1 µg TDENV-PIV with AS03B1 adjuvant; 0.5 mL intramuscular injection at 0 and 28 days
干预措施: 1 µg TDENV-PIV with AS03B1 adjuvant (Biological)
Placebo
Phosphate buffered saline; 0.5 mL intramuscular injection at 0 and 28 days
干预措施: Phosphate buffered saline (Other)
TDENV-PIV alum1
1 µg TDENV-PIV with Alum adjuvant; 0.5 mL intramuscular injection at 0 and 28 days
干预措施: 1 µg TDENV-PIV with Alum adjuvant (Biological)
结局指标
主要结局
Number of Subjects With Adverse Events Within the 28 Day Follow-up
时间窗: Days 0-28
Number of subjects with adverse events occurring within days 0-28 following vaccination
Incidence of Any Symptoms (Solicited and Unsolicited) Reported During the 7-day Post Vaccination Period. Total Vaccinated Cohort (TVC)
时间窗: Days 0-6 post vaccination
Overall incidence of any symptoms (solicited and unsolicited) reported during the 7-day (days 0-6) post vaccination period in TVC population
Incidence of General Symptoms (Solicited and Unsolicited) Reported During the 7-day Post Vaccination Period, Total Vaccinated Cohort (TVC)
时间窗: Days 0-6 post vaccination
Incidence of General Symptoms (Solicited and Unsolicited) Reported during the 7-day Post Vaccination Period for TVC population. General symptoms are described as fatigue, gastrointestinal symptoms, headache, joint pain, muscle aches and increased temperature (oral).
Incidence of Local Symptoms (Solicited and Unsolicited) Reported During the 7-day Post Vaccination Period, Total Vaccinated Cohort (TVC)
时间窗: Days 0-6 post vaccination
Incidence of Local Symptoms (Solicited and Unsolicited) Reported during the 7-day Post Vaccination Period in TVC population. Local symptoms are described as pain, redness and swelling.
Summary of Subjects With Serious Adverse Events
时间窗: days 0-392
Summary of subjects with serious adverse events through out the study
次要结局
- Geometric Mean Titers (GMTs) of Neutralizing Antibody Titers Specific to Each DENV Type - According to Protocol Population (ATP)(up to month 13)
- Number of Subject Showing Monovalent, Bivalent, Trivalent and Tetravalent Response for Neutralizing Antibodies - Total Vaccinated Cohort (TVC)(up to month 13)
- Number of Subjects With Laboratory Values Within and Outside the Normal Ranges and With Different Grade of Adverse Event From Screening to Day 56 Visit(day 56 visit)