A Phase I, Randomized, Placebo-Controlled, Observer-blind, Two-dose (0-28 Day Schedule) Primary Vaccination Study of WRAIR Tetravalent Dengue Virus Purified Inactivated Vaccine (TDENV-PIV) in Healthy Adults in Puerto Rico
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
- Safety and reactogenicity of various TDENV-PIV formulations from Day 0 through 28 days after the second dose (Day 0 - Day 56)
研究概览
简要总结
This is a first time in humans (FTiH) study designed to assess the experimental TDENV-PIV vaccine in a predominantly dengue-primed adult population. The study is designed to afford a first time in humans (FTiH) safety and immunogenicity assessment of three TDENV-PIV vaccine candidates, each formulated with a different adjuvant: either aluminum hydroxide, AS01E or AS03B (adjuvants used in 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. There is a parallel FTiH study that is conducted in the United States in a dengue-naive population using the same investigational vaccines.
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
- 20 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 20 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
- •Subject has lived in the Caribbean for more than 10 years
- •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).
- •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 Exclusion:
- •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)
- •Previous or planned administration of any other flavivirus vaccine (approved or investigational) for the entire study duration
- •Previous receipt of any investigational dengue virus vaccine
- •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 normal limits for their age, gender, and locality at screening.
结局指标
主要结局
Safety and reactogenicity of various TDENV-PIV formulations from Day 0 through 28 days after the second dose (Day 0 - Day 56)
时间窗: Up to Day 56
Safety and Reactogenicity: * Occurrence, intensity and relationship to vaccination of solicited local and general adverse events (AEs) during the 7-day follow-up period post each vaccination (Day 0-6) * Occurrence, intensity and relationship to vaccination of unsolicited AEs during the 28-day follow-up period post each vaccination (Day 0-27) * Hematological and biochemical levels at study visits on Days 0, 7, 28, 35 and 56 * Occurrence of serious adverse events (SAEs) from Day 0 to Day 56 * Occurrence of potential immune-mediated diseases (pIMDs) and medically attended AEs from Day 0 to Day 56
Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations 28 days after the second dose (Day 56)
时间窗: Day 56
Humoral Immunogenicity: Neutralizing antibody titers specific to each DENV type at Day 56 * Geometric mean titers (GMTs) of neutralizing antibody titers to each DENV type * Rate of fold increases in neutralizing antibody from Day 0 for each DENV type * Seropositivity rates for each DENV type * Trivalent and tetravalent seropositivity rates
次要结局
- Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations on Days 0, 7 and 28 and Months 7 and 13(Up to month 13)
- Safety of various TDENV-PIV formulations, from Day 0 to Month 13 (Visits 1-11)(Up to month 13)
- • To evaluate the safety of various TDENV-PIV formulations from Month 14 through the end of the study (Visit 15)(Up to the end of study (Month 37-39))