Phase I Evaluation of the Safety and Immunogenicity of the Live Attenuated Zika Vaccine rZIKV/D4Δ30-713 in Flavivirus-naïve Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 2
- 主要终点
- Number of Participants With Solicited Local and General Adverse Events (AEs)
研究概览
简要总结
This is a phase 1 double-blind, placebo controlled trial designed to evaluate the safety, reactogenicity, and immunogenicity of a single dose of the live attenuated Zika vaccine rZIKV/D4Δ30-713 in adults with no history of previous flavivirus infection.
详细描述
Fifty-six healthy volunteers will be enrolled over 2 sequential cohorts:
Cohort 1: n=28, volunteers will be randomly assigned to a single dose of either vaccine (10^3 PFU, n=20) or placebo (n=8). Cohort 1 will be enrolled and evaluated first. If the vaccine is not found to induce seroconversion to ZIKV in > 80% of subjects inoculated with 10-^3 PFU of the vaccine, a second cohort of volunteers will be enrolled and will be inoculated with 10^4 PFU of vaccine (or placebo).
Cohort 2: n=28, volunteers will be randomly assigned to a single dose of either vaccine (10^4 PFU, n=20) or placebo (n=8).
All volunteers will be followed on an outpatient basis for 6 months following vaccination (13 follow up visits over 180 days). Follow up visits will include clinical assessments as well as sample collection for evaluation of viremia and seroconversion. Sample collection will include blood, urine, saliva, nasopharyngeal or midturbinate swab, vaginal secretion or semen collection on specified visit days throughout the 180 day follow up period.
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult male or female between 18 and 50 years of age, inclusive.
- •Good general health as determined by physical examination, laboratory screening, and review of medical history.
- •Available for the duration of the study, which is approximately 26 weeks.
- •Willingness to participate in the study as evidenced by signing the informed consent document.
- •Females only: Female subjects of childbearing potential, with the exception noted below, should be willing to use effective contraception and have no plans to undergo IVF (in vitro fertilization) during participation in the trial. Reliable methods of contraception include hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, and intrauterine device. Women must have been on an effective method of birth control for at least 30 days prior to enrollment. All female subjects will be considered as having childbearing potential, except for women who exclusively have sex with women, those who have had a hysterectomy, tubal ligation, or tubal coil (at least 3 months prior to vaccination), or are considered to be post-menopausal, as documented by at least 1 year since last menstrual period with a follicle-stimulating hormone (FSH) level in the menopausal range or at least 24 consecutive months of amenorrhea. Transgender men who have internal female organs and have sex with men will be considered of childbearing potential and should be willing to use effective contraception during the trial. Exception: Females who have sex with females (exclusively) and have no intention of conceiving a child during the study and women whose partners have had a vasectomy will not be required to use contraception, however they will be required to use female condoms and/or dental dams for at least 1 month following vaccination. For women whose sexual partner has had a vasectomy, the vasectomy must have been performed 30 days or more prior to enrollment.
- •Males only: Males of reproductive potential should be willing to use barrier contraception for the first 3 months following vaccination* and agree to not donate sperm for the duration of the study.
- •Based on CDC guidance for men returning from ZIKV-endemic areas
排除标准
- •Females only: Currently pregnant, as determined by positive β-human choriogonadotropin (HCG) test, or breast-feeding.
- •Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease based on history, physical examination, and/or laboratory studies.
- •Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the subject's ability to understand and cooperate with the requirements of the study protocol.
- •Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in this protocol.
- •Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, or would render the subject unable to comply with the protocol.
- •Any significant alcohol or drug abuse in the past 12 months that has caused medical, occupational, or family problems, as indicated by subject history.
- •History of a severe allergic reaction or anaphylaxis.
- •Severe asthma (emergency room visit or hospitalization within the last 6 months).
- •HIV infection, as indicated by screening and confirmatory assays.
- •Hepatitis C virus (HCV) infection, as indicated by screening and confirmatory assays.
- •Hepatitis B virus (HBV) infection, as indicated by hepatitis B surface antigen (HBsAg) screening.
- •Any known immunodeficiency syndrome.
- •History of Guillain-Barrè syndrome.
- •Current use of anticoagulant medications (this does not include anti-platelet medication such as aspirin or non-steroidal anti-inflammatory medications).
- •Use of immunosuppressive corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 28 days prior to or following inoculation. An immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg of a prednisone equivalent per day for greater than or equal to 14 days.
- •Receipt of a live vaccine within 28 days or a killed vaccine within 14 days prior to inoculation, or anticipated receipt of any vaccine during the 28 days following inoculation with the exception of COVID-19 vaccines either licensed or under EUA which can be given at any time, however all effort will be made to avoid giving COVID-19 vaccines within the above windows.
- •Asplenia.
- •Receipt of blood products within the past 6 months, including transfusions or immunoglobulin, or anticipated receipt of any blood products or immunoglobulin during the 28 days following inoculation.
- •History or serologic evidence of previous ZIKV or other flavivirus infection (e.g., dengue, yellow fever virus, St. Louis Encephalitis virus, or West Nile virus).
- •Previous receipt of a flavivirus vaccine (licensed or experimental).
- •Receipt or anticipated receipt of any investigational agent in the 28 days before or after inoculation with the exception of COVID-19 vaccines, either licensed or authorized under EUA.
- •Refusal to allow specimen storage for future research.
- •Is in isolation or quarantine for SARS-CoV-2 infection or exposure and cannot complete screening or enrollment for this reason.
研究组 & 干预措施
Cohort 1: Vaccine
Single dose of rZIKV/D4Δ30-713 (10^3 PFU) via subcutaneous injection (0.5ml).
干预措施: Single dose of rZIKV/D4Δ30-713 (10^3 PFU) via subcutaneous injection (0.5ml) (Biological)
Cohort 1 - Placebo
Single dose of placebo via subcutaneous injection (0.5ml).
干预措施: Single dose of placebo via subcutaneous injection (0.5ml). (Biological)
Cohort 2 - Vaccine
Single dose of rZIKV/D4Δ30-713 (10^4 PFU) via subcutaneous injection (0.5ml).
干预措施: Single dose of rZIKV/D4Δ30-713 (10^4 PFU) via subcutaneous injection (0.5ml) (Biological)
Cohort 2 - Placebo
Single dose of placebo via subcutaneous injection (0.5ml).
干预措施: Single dose of placebo via subcutaneous injection (0.5ml). (Biological)
结局指标
主要结局
Number of Participants With Solicited Local and General Adverse Events (AEs)
时间窗: Solicited AE's assessed every visit through Day 28
Evaluated using the Adverse Event Grading Table in the study protocol.
To Determine the Immunogenicity of a Single Dose of rZIKV/D4Δ30-713
时间窗: Measured through Day 28
Determination of the serum plaque reduction neutralization titer 50% (PRNT50) to ZIKV for each subject at Study Day 28 post-inoculation. Seroconversion will be defined as achieving a PRNT50 ≥ 1:10 at any time-point through Study Day 28. The peak PRNT50 to ZIKV through Study Day 28 will be calculated for each subject included in the per-protocol an intent-to-treat analysis and the geometric mean peak titer for vaccinated subjects will be calculated.
次要结局
- Viremia Induced by Vaccine (Number of Participants With Detectable Virus at Any Time Point)(Measured through Day 90)
- Number of Vaccinees Infected With rZIKV/D4Δ30-713(Measured through Day 180)
- Immunogenicity of rZIKV/D4Δ30-713 in Flavivirus-naïve Subjects(Measured through Day 180)
- Durability of Antibody Response(26 Weeks post vaccination)
- Quantity and Duration of ZIKV Presence(90 days post vaccination)