An Experimental Medicine Decipher of a Minimum Correlate of Cellular Immunity
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Viremia levels after second vaccination
研究概览
简要总结
We hypothesize that a high CD4+ and CD8+ T cell count will reduce viremia upon challenge with a structurally heterologous virus, and correspondingly result in reduced magnitude of host response to challenge infection.
Primary Objective: To compare, after challenge with a structurally heterologous vaccine, the differences in levels of viremia between healthy adults who received primary vaccination with either YF17D vaccine, chimeric JE-YF17D vaccine, or inactivated JE vaccine.
58 subjects will be randomised into 1 of 2 arms (Arm B1 and Arm B2) in a 1:1 ratio, in a double-blind fashion. Subjects in Arm B1 will receive JE-YF17D vaccine (Imojev, Sanofi Pasteur) on Day 0 followed by YF17D vaccine (Stamaril, Sanofi Pasteur) on Day 28. Subjects in Arm B2 will receive Stamaril on Day 0 followed by Imojev on Day 28. Arm B3 will be conducted as a separate single-arm open label design in 14 subjects. Subjects in Arm B3 will receive inactivated JE vaccine (Ixiaro, Valneva) on Day 0 followed by Stamaril on Day 28.
The rationale for these three study arms is as follows: Arm B1 will show the impact low levels of viremia, and the resultant low levels of virus-specific CD4+ and CD8+ T cells, would have on YF17D infection. In contrast, YF17D vaccination in Arm B2 would produce high levels of viremia, and in turn high levels virus-specific T cells, thus likely ameliorating JE-YF17D infection. Arm B3 will serve as the control arm, as vaccination with inactivated JE vaccine would not produce any YF17D-specific T cell response. Notably, the first vaccination in Arms B1 and B2 would also provide the viremia response in the absence of virus-specific T cells, which would serve as a reference point to interpret the outcome of the second vaccination.
详细描述
Criteria for Recruitment and Recruitment Process: Subjects will be recruited from SingHealth Investigational Medicine Unit (IMU) healthy volunteer database and recruitment posters. Subjects will be given a copy of the Participant Information and Informed Consent Form to read upon their arrival. A briefing session on the study will be conducted by the Investigator. Thereafter, subjects will be ushered into a private room where informed consent is obtained and where questions about the study can be asked freely. Subjects will not be rushed into making a decision to participate in the study. They will be encouraged to speak to their family members about participation in the study; and allowed to defer their decision (without any prejudice) to participate till after discussion with their family members.
Screening Visits and Procedures: Subjects will be recruited via the SingHealth Investigational Medicine Unit (IMU). Informed written consent will be sought from subjects who fulfill criteria for enrollment. All consented subjects will undergo screening, which includes physical examination, full blood count, liver function test, anti-dengue antibodies ELISA (Enzyme-Linked Immunosorbent Assay) and urinary pregnancy test (for female subjects of child-bearing potential).
A urine pregnancy test will be performed at screening and on the day of vaccination (day 0 and day 28) for female subjects of child-bearing potential. Only those with a negative urine pregnancy test will be considered to be eligible for the study, provided that other eligibility criteria were fulfilled.
Both male (if he has a partner of childbearing potential) and female subjects (of childbearing potential) must agree to use adequate and reliable contraceptive measures (e.g. spermicides, condoms, contraceptive pills) or practice abstinence for 10 days after vaccination.
Study Visits and Procedures: 58 subjects will be randomised into 1 of 2 arms (Arm B1 and Arm B2) in a 1:1 ratio, in a double-blind fashion. Subjects in Arm B1 will receive JE-YF17D vaccine (Imojev, Sanofi Pasteur) on Day 0 followed by YF17D vaccine (Stamaril, Sanofi Pasteur) on Day 28. Subjects in Arm B2 will receive Stamaril on Day 0 followed by Imojev on Day 28. Arm B3 will be conducted as a separate single-arm open label design in 14 subjects. Subjects in Arm B3 will receive inactivated JE vaccine (Ixiaro, Valneva) on Day 0 followed by Stamaril on Day 28. Study visits in all arms will occur on Day 0, 4, 7, 10, 14, 28, 29, 32, 35, 38, 42, 58. At each study visit, physical examination, vital signs and research blood sampling will be performed. On Day 0 and Day 28, blood sampling will be performed prior to vaccination.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Arms B1 and B2 will be double-blinded. Arm B3 will be open label.
入排标准
- 年龄范围
- 21 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adults, 21-45 years of age at time of screening
- •Willing to comply to study procedures and adhere to study schedule visits.
- •Satisfactory baseline medical assessment as assessed by physical examination and a stable health status. The laboratory values must be within the normal range of the assessing site or show abnormalities that are deemed not clinically significant as judged by the investigator. A stable health status is defined as the absence of a health event satisfying the definition of a serious adverse event.
- •Accessible vein for blood collection.
- •Ability to provide informed consent.
- •Female subjects of non-child bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Post-menopausal subjects must have had at least 12 months of natural (spontaneous) amenorrhea
- •Female subjects of child bearing potential with negative urine pregnancy tests on the day of screening and vaccination.
- •Both male (if he has a partner of childbearing potential) and female subjects (of childbearing potential) must agree to use adequate and reliable contraceptive measures (e.g. spermicides, condoms, contraceptive pills) or practice abstinence for 10 days after vaccination.
排除标准
- •History of presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, haematological, endocrine or immunosuppressive disorders that would be a risk factor when administered the investigational product (IP)
- •Previous receipt of Imojev, Stamaril or Ixiaro vaccines, or any other yellow fever or Japanese encephalitis vaccines
- •Previous history of Yellow fever virus or Japanese encephalitis infection
- •Known allergy to Imojev, Stamaril or Ixiaro vaccines or their components
- •History of severe food/drug/vaccine allergies e.g. angioedema, anaphylaxis
- •Known allergy to egg or egg products
- •History of thymus gland disease
- •Diagnosed with cancer or on treatment for cancer (with the exception of localized basal cell carcinoma) within 3 years prior to screening
- •Evidence of clinically significant anemia (Hb <10 g/dl)
- •Blood donation exceeding >450mls in the past 3 months
- •Presence of acute infection in the preceding 7 days or presence of a temperature ≥ 38.0°C (oral or tympanic temperature assessment), or acute symptoms greater than of "mild" severity on the scheduled date of first dose
- •Woman who is pregnant or breast feeding
- •Evidence of substance abuse, or previous substance abuse including alcohol
- •Participation in a study involving administration of an investigational compound (including investigational vaccines) within the past three months, or planned participation during the duration of this study.
- •Receipt of anti-inflammatory drugs (such as NSAIDs or systemic steroids) in the past 7 days.
- •Receipt of any licensed vaccine in the past 30 days before the first study vaccine dose.
- •Positive serum Dengue IgG by ELISA
- •Any condition that, in the opinion of the investigator, would complicate or compromise the study or wellbeing of the subject.
结局指标
主要结局
Viremia levels after second vaccination
时间窗: Day 0 to Day 58
Viremia level (genome copies/ml) after second vaccination with either JE-YF17D or YF17D
次要结局
- T cell responses after vaccination(Day 0 to Day 58)
- Viremia level after first vaccination(Day 0 to Day 58)
- Duration of viremia after second vaccination(Day 0 to Day 58)
- Antibody Titres(Day 0 to Day 58)
- Rates of Adverse Events(Day 0 to Day 58)