A Phase 1, Randomized, Open-label, Single-center, Study of TDENV-PIV and LAV Dengue Vaccine Platforms as Part of a Heterologous Prime-boost Strategy in Healthy Adults in a Nonendemic Region
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Number of unsolicited adverse events
研究概览
简要总结
The potential synergistic effect of administering 2 dengue vaccine candidates that were previously shown to be safe and immunogenic in humans will be evaluated in this study. A prime-boost study of tetravalent dengue virus purified inactivated vaccine (TDENV-PIV) with alum and tetravalent dengue live attenuated virus (TDENV-LAV) vaccine Formulation 17 (F17) will gather data to help better understand the human immune response to dengue vaccination and infection.
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
- None
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female between 18 and 49 years of age (inclusive) at the time of consent
- •Able to provide written informed consent
- •Healthy as established by medical history and clinical examination before entering into the study
- •Able and willing to comply with the requirements of the protocol (eg, document events in memory aid, return for follow-up visits, etc.)
- •Female subject of non-childbearing potential (non-childbearing potential is defined as having either a current tubal ligation at least 3 months prior to enrollment or a history of a hysterectomy, ovariectomy, or is post-menopause)
- •Female subject is not breastfeeding and agrees not to breastfeed for 3 months after last vaccination
- •Female subject of childbearing potential may be enrolled in the study, if the subject has:
- •Practiced adequate contraception for 30 days prior to vaccinations, and
- •A negative urine pregnancy test on each day of vaccination, and
- •Agreed to continue adequate contraception until 3 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 during the period starting 30 days preceding the first dose of study vaccine 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 dose
- •For corticosteroids, this will mean prednisone ≥ 20 mg/d 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 14 days before or after each scheduled dose of an investigational product
- •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 or related to a study procedure
- •Major congenital defects or serious chronic illness
- •History of any neurological disorders or seizures. (except for a childhood febrile seizures)
- •Acute disease and/or fever (oral body temperature ≥ 100.4°F/38.0°C) at the time of enrollment (a subject with a minor illness, ie, 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 or planned administration during the study period
- •History of chronic alcohol and/or drug abuse
- •Pregnant or breastfeeding 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 prior to the study end for the participant
- •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:
- •> 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)
- •Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.
研究组 & 干预措施
Group 1: LAV (T=0), PIV (T=28)
Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 0 of the study.
Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 28 of the study.
干预措施: TDENV-LAV (Biological)
Group 1: LAV (T=0), PIV (T=28)
Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 0 of the study.
Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 28 of the study.
干预措施: TDENV-PIV 4 µg + alum adjuvant (Biological)
Group 2: PIV (T=0), LAV (T=28)
Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 0 of the study.
Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 28 of the study.
干预措施: TDENV-LAV (Biological)
Group 2: PIV (T=0), LAV (T=28)
Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 0 of the study.
Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 28 of the study.
干预措施: TDENV-PIV 4 µg + alum adjuvant (Biological)
Group 3: LAV (T=0), PIV (T=180)
Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 0 of the study.
Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 180 of the study.
干预措施: TDENV-LAV (Biological)
Group 3: LAV (T=0), PIV (T=180)
Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 0 of the study.
Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 180 of the study.
干预措施: TDENV-PIV 4 µg + alum adjuvant (Biological)
Group 4: PIV (T=0), LAV (T=180)
Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 0 of the study.
Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 180 of the study.
干预措施: TDENV-LAV (Biological)
Group 4: PIV (T=0), LAV (T=180)
Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 0 of the study.
Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 180 of the study.
干预措施: TDENV-PIV 4 µg + alum adjuvant (Biological)
结局指标
主要结局
Number of unsolicited adverse events
时间窗: 28 days after each vaccination
Number of solicited adverse events
时间窗: 21 days after each vaccination
Number of hematological and biochemistry abnormalities
时间窗: 7 and 28 days and each vaccination
Number of serious adverse events
时间窗: Day 208 or day 360
Number of medically attended adverse events
时间窗: Day 208 or day 360
Number of potential immune-mediated diseases
时间窗: Day 208 or day 360
次要结局
- Microneutralizing (MN) dengue antibody titers(Up to 1 year)