Inactivated Bivalent Enterovirus Vaccine Phase I/II Clinical Trial: Open-Label Observation in Healthy Adults and Children, and Randomized, Double-Blind, Controlled Clinical Trial in Children
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 744
- 试验地点
- 1
- 主要终点
- Phase Ⅰ: Based on adverse events, evaluate the safety of the trial vaccine among participants in different age groups
研究概览
简要总结
The Phase I clinical trial is divided into two parts. The first part uses an open-label design, while the second part uses a randomized, double-blind, and controlled design. The goal of this clinical trial is to evaluate the tolerability and safety of a bivalent (EV71/CA16, Enterovirus 71/Coxsackievirus A16) inactivated enterovirus vaccine (Vero cell) developed by Sinovac. The vaccine will be administered to healthy adults, children aged 6 to 12 years, and children aged 6 to 71 months.
The Phase II clinical trial will also use a randomized, double-blind, and controlled design to evaluate the safety and immunogenicity of the same bivalent inactivated enterovirus vaccine (Vero cell) developed by Sinovac. This trial will involve healthy children aged 6 to 71 months.
详细描述
For phase I clinical trial:
The first part of the trial plans to recruit thirty-six healthy adults aged 18-59 years and thirty-six children aged 6-12 years, with twelve participants in each of the low-dose (EV71 480 U-CA16 600 SU/0.5 ml), medium-dose (EV71 960 U-CA16 600 SU/0.5 ml), and high-dose (EV71 1920U-CA16 1200SU/0.5ml) experimental groups. The participants will receive two doses of the experimental vaccine according to a 0-1-month schedule, with adults vaccinated before children.
The second part of the trial plans to recruit seventy-two healthy children aged 6-71 months, with each dose group having twelve participants in the 6-23 months and 24-71 months age groups. The participants will receive two doses of the experimental vaccine according to a 0-1-month schedule, with each dose group being randomized, double-blind, and positive-controlled. The vaccine will be compared to a control (EV71 vaccine) at each dose level.
The dose escalation principle within each age group is from low to high doses: After completing the first dose of the lower dose stage, a safety observation period of 0-7 days will be conducted to confirm safety based on adverse event occurrence and blood routine, blood biochemistry, and urine routine tests (if any) before proceeding to the higher dose stage. The sequential enrollment principle between different age groups is from adults and children aged 6-12 years to children aged 6-71 months. After the first dose of each dose group is administered to adults, children aged 6-12 years in the same dose group can be enrolled only after a safety observation period of 0-7 days confirms safety. After completing the second dose of the medium-dose group in adults, vaccination of children aged 6-71 months can begin.
Participants in the adult and children aged 6-12 years groups will have approximately 5.5 mL of blood (2.0 mL anticoagulated blood and 3.5 mL non-anticoagulated blood) and about 2-10 mL of urine samples collected before and on day three after each dose for blood routine, blood biochemistry, and urine routine tests to evaluate vaccine safety. Only participants aged 24-71 months in the second stage of the trial will undergo these tests before the first dose. Whether participants aged 24-71 months to conduct tests on days 3 (Visit2), 30 (Visit5), and 33 (Visit6) will depend on the relevant test results in the children aged 6-12 years group. If 10% of participants in each dose stage of the children aged 6-12 years group have abnormal test results related to the vaccine that is clinically significant after the first dose, blood and urine samples will be collected from corresponding dose stage participants aged 24-71 months on days 3 (Visit2), 30 (Visit5), and 33 (Visit6).
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
- 6 Months 至 59 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants aged 18-59 years, 6-12 years, and 6-71 months.
- •Participants and/or their guardians can understand and voluntarily sign the informed consent form (participants aged 8-12 years require dual signatures from both participants and their guardians).
- •Willing and able to comply with all visit schedules, sample collection, vaccine administration, and other trial procedures.
- •Provide legal identification of the participants and/or their guardians.
排除标准
- •History of hand, foot, and mouth disease or EV71 vaccination.
- •Known severe allergy to the vaccine or vaccine components, such as urticaria, respiratory distress, and angioedema.
- •Congenital abnormalities or developmental disorders, genetic defects (such as Down syndrome, thalassemia, or G6PD deficiency), severe malnutrition, etc.
- •Based on medical history and physical examination, the presence of severe chronic diseases, severe cardiovascular diseases, uncontrolled hypertension or diabetes, liver or kidney diseases, etc.
- •Based on medical history and physical examination, the presence of autoimmune diseases, immunodeficiency diseases, and/or blood diseases (including but not limited to systemic lupus erythematosus, ankylosing spondylitis, thyroidectomy, autoimmune thyroid disease, any form of malignancy, asplenia, functional asplenia).
- •Based on medical history and physical examination, abnormal coagulation function (such as coagulation factor deficiency, coagulation disorders, platelet abnormalities) or obvious bruising or bleeding disorders.
- •Based on medical history and physical examination, the presence of severe neurological diseases (epilepsy, convulsions, or seizures), mental illness, or corresponding family history.
- •Long-term use (more than 14 days) of corticosteroids or other immunosuppressive agents (excluding corticosteroid sprays for allergic rhinitis and surface corticosteroid treatment for acute non-complicated dermatitis) or cytotoxic therapy or planning to receive such treatment during the trial.
- •History of long-term alcohol abuse or drug abuse.
- •Females who are breastfeeding, pregnant, or planning to become pregnant within 90 days, or females with positive pregnancy test results. Note: male participants whose spouse plans to become pregnant within 90 days are also included.
- •Received immunoglobulin and/or other blood products in the past 3 months or planning to receive such treatment during the trial.
- •Received other investigational drugs or vaccines within the past 30 days or planning to receive such drugs or vaccines during the trial.
- •Vaccinated with attenuated live vaccines within the past 14 days or subunit or inactivated vaccines within the past 7 days.
- •Suspected or confirmed fever within 72 hours before vaccination or axillary temperature >37.0℃ on the day of vaccination.
- •Clinical laboratory testing shows laboratory abnormalities beyond the reference range and with clinical significance (applicable only to Phase I clinical trials for adults/6-12-year-old children/24-71-month-old children):
- •A. Complete blood count: white blood cell count, hemoglobin, platelet count.B. Blood biochemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), creatinine (CR), fasting blood glucose (Glu).C. Urine routine: urine protein (PRO).
- •Any acute illness (with or without fever) or exacerbation of chronic illness within the past 7 days.
- •According to the investigator's judgment, there are any other factors that make the participant unsuitable for participation in the clinical trial.
研究组 & 干预措施
low-dose experimental group
phase Ⅰ: 18~59 years old,6~12 years old,6~71 months old; phase Ⅱ：6~71 months old
干预措施: low dose Bivalent Enterovirus Vaccine (Vero Cell), Inactivated (Biological)
medium-dose experimental group
phase Ⅰ: 18~59 years old,6~12 years old,6~71 months old; phase Ⅱ：6~71 months old
干预措施: medium dose Bivalent Enterovirus Vaccine (Vero Cell), Inactivated (Biological)
high-dose experimental group
phase Ⅰ: 18~59 years old,6~12 years old,6~71 months old; phase Ⅱ：6~71 months old
干预措施: high dose Bivalent Enterovirus Vaccine (Vero Cell), Inactivated (Biological)
Active control group
phase Ⅰ: 6~71 months old; phase Ⅱ：6~71 months old
干预措施: Enterovirus type EV71 vaccine (Vero cell), Inactivated (Biological)
结局指标
主要结局
Phase Ⅰ: Based on adverse events, evaluate the safety of the trial vaccine among participants in different age groups
时间窗: 30 days
the incidence rates of adverse reactions from the start of vaccination to 30 days after the end of the entire vaccination course
Phase Ⅱ: Evaluate the immunogenicity of the trial vaccine in the target population.
时间窗: 30 days
The seroconversion rate of EV71 and CA16 neutralizing antibodies in children aged 6-71 months 30 days after the end of the entire vaccination course.
次要结局
- Phase Ⅱ: Based on adverse events, evaluate the safety of the trial vaccine.(6 months)
- Phase Ⅰ: Based on laboratory abnormalities, evaluate the safety of the trial vaccine among participants in different age groups.(3 days)
- Phase Ⅱ: Evaluate other immunogenicity indicators of the trial vaccine.(30 days)
- Phase Ⅱ: Evaluate the immune persistence of the trial vaccine.(6 months)
- Phase Ⅰ: Based on adverse events, evaluate the safety of the trial vaccine among participants in different age groups.(7 days)
- Phase Ⅱ: Based on adverse events, evaluate the safety of the trial vaccine.(30 days)
- Phase Ⅱ: Based on adverse events, evaluate the safety of the trial vaccine.(7 days)
- Phase Ⅰ: Based on adverse events, evaluate the safety of the trial vaccine among participants in different age groups.(6 months)