中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2200065082
最近更新日期： Date of Last Refreshed on：	2023-06-20 21:12:10
注册时间： Date of Registration：	2022-10-27 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	评价四价流感病毒裂解疫苗（MDCK细胞）接种于3岁及以上人群安全性的单中心、盲法、阳性疫苗和安慰剂对照的Ⅰ期临床试验
Public title：	Single center, blind, positive vaccine and placebo controlled phase I clinical trial to evaluate the safety of bivalent influenza virus split vaccine (MDCK cells) in people aged 3 years and above
注册题目简写：
English Acronym：
研究课题的正式科学名称：	评价四价流感病毒裂解疫苗（MDCK细胞）接种于3岁及以上人群安全性的单中心、盲法、阳性疫苗和安慰剂对照的Ⅰ期临床试验
Scientific title：	Single center, blind, positive vaccine and placebo controlled phase I clinical trial to evaluate the safety of bivalent influenza virus split vaccine (MDCK cells) in people aged 3 years and above
研究课题代号(代码)： Study subject ID：
在二级注册机构或其它机构的注册号： The registration number of the Partner Registry or other register：

申请注册联系人：	张家友	研究负责人：	张丽
Applicant：	Jiayou Zhang	Study leader：	Li Zhang
申请注册联系人电话： Applicant telephone：	+86 15207190297	研究负责人电话： Study leader's telephone：	+86 18615281727
申请注册联系人传真： Applicant Fax：	+86 027 86634151	研究负责人传真： Study leader's fax：	+86 0531 82620031
申请注册联系人电子邮件： Applicant E-mail：	tjzhjy@126.com	研究负责人电子邮件： Study leader's E-mail：	zl9127@163.com
申请单位网址(自愿提供)： Applicant website(voluntary supply)：		研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：
申请注册联系人通讯地址：	湖北省武汉市江夏区郑店街黄金工业园路1号	研究负责人通讯地址：	山东省济南市经十路16992号
Applicant address：	1 Gold Industrial Park Road, Zhengdian Street, Jiangxia District, Wuhan, Hubei	Study leader's address：	16992 Jingshi Road, Jinan, Shandong
申请注册联系人邮政编码： Applicant postcode：		研究负责人邮政编码： Study leader's postcode：
申请人所在单位：	武汉生物制品研究所有限责任公司
Applicant's institution：	Wuhan Institute of Biological Products Co., Ltd.
研究负责人所在单位：	山东省疾病预防控制中心
Affiliation of the Leader：	Shandong Provincial Center for Disease Control and Prevention

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	伦研批第（SDJK2022-36-01)号	伦理委员会批件附件： Approved file of Ethical Committee：	查看附件View
批准本研究的伦理委员会名称：	山东省疾病预防控制中心医学伦理委员会
Name of the ethic committee：	Institutional Reriew Board of Shandong Center for Disease Control and Prevention
伦理委员会批准日期： Date of approved by ethic committee：	2022-08-30 00:00:00
伦理委员会联系人：	张曼
Contact Name of the ethic committee：	Man Zhang
伦理委员会联系地址：	山东省济南市经十路16992号
Contact Address of the ethic committee：	16992 Jingshi Road, Jinan, Shandong
伦理委员会联系人电话： Contact phone of the ethic committee：		伦理委员会联系人邮箱： Contact email of the ethic committee：

研究实施负责（组长）单位：

山东省疾病预防控制中心

Primary sponsor：

Shandong Provincial Center for Disease Control and Prevention

研究实施负责（组长）单位地址：

山东省济南市经十路16992号

Primary sponsor's address：

16992 Jingshi Road, Jinan, Shandong

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	湖北	市(区县)：	武汉
Country：	China	Province：	Hubei	City：	Wuhan
单位(医院)：	武汉生物制品研究所有限责任公司	具体地址：	湖北省武汉市江夏区郑店街黄金工业园路1号
Institution hospital：	Wuhan Institute of Biological Products Co., Ltd.	Address：	1 Gold Industrial Park Road, Zhengdian Street, Jiangxia District, Wuhan, Hubei

经费或物资来源：

企业自有资金

Source(s) of funding：

Enterprise's own funds

研究疾病：

四价流感病毒裂解疫苗（MDCK细胞）相关型别的流感病毒引起的流行性感冒

Target disease：

Influenza caused by quadrivalent influenza virus split vaccine (MDCK cell) -associated influenza viruses

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

I期临床试验

Study phase：

1

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

主要目的：评价四价流感病毒裂解疫苗（MDCK细胞）在3岁及以上人群中接种的安全性。次要目的：评价四价流感病毒裂解疫苗（MDCK细胞）在3岁及以上人群中接种的免疫原性。探索性目的：探索3-8岁人群以不同免疫程序接种四价流感病毒裂解疫苗（MDCK细胞）的免疫原性。

Objectives of Study：

Main purpose: To evaluate the safety of bivalent influenza virus split vaccine (MDCK cells) in people aged 3 years and above. Secondary purpose: To evaluate the immunogenicity of tetravalent influenza virus split vaccine (MDCK cells) in people aged 3 years and above. Exploratory purpose: To explore the immunogenicity of trivalent influenza virus split vaccine (MDCK cells) inoculated in different immunization programs for people aged 3-8 years.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1. Volunteers aged 3-8:
(1) The applicant should be 3 years old or less than 9 years old on the enrollment day, and be able to provide valid identification of the volunteer and his/her guardian;
(2) Guardians of volunteers have the ability to understand the requirements and process of the study, agree to participate in the clinical trial and sign the informed consent (8-year-old volunteers also need to sign the informed consent for minors);
(3) The guardians of the volunteers have the ability to understand the study procedures and attend all planned follow-up visits;
(4) Axillary temperature < 37.3 degree on the day of enrollment;
(5) No influenza vaccine in any epidemic season before enrollment.
2. Volunteers aged 9-59:
(1) Over 9 years of age and under 60 years of age on the day of enrollment, who can provide valid identification of the volunteer and/or his/her guardian;
(2) The volunteers and/or their guardians have the ability to understand the study requirements and process and agree to participate in the clinical trial, and the underage volunteers sign the underage informed consent, and their guardians sign the informed consent;
(3) The volunteers and/or their guardians have the ability to understand the study procedures and attend all planned follow-up visits;
(4) Axillary temperature on the day of enrollment, < 37.3 degree;
(5) Have not received influenza vaccine in the past 2 years (from 2021 to now);
(6) Negative urine pregnancy test (applicable to female volunteers of childbearing age);
(7) Non-pregnancy and non-lactation period of female volunteers of childbearing age;
(8) Agree to take effective contraceptive measures, no pregnancy plan and birth plan during the study (applicable to fertile volunteers (women of childbearing age, men of eligible age) and male volunteers whose partners are women of childbearing age).
3. Volunteers >=60 years old:
(1) At least 60 years old on the enrollment day, and can provide valid identification;
(2) Ability to understand research requirements and process, agree to participate in clinical trials, and sign informed consent;
(3) Ability to understand study procedures and attend all planned follow-up visits;
(4) Axillary temperature < 37.3 degree on the day of enrollment;
(5) Have not received influenza vaccine in the past 2 years (from 2021 to now);
(6) Agree to use effective contraception, no pregnancy and no family planning during the study (for male volunteers with female partners of reproductive age).

排除标准：

1. 免前实验室检测指标存在异常，且经临床医生判定异常有临床意义者；
2. 在研究期间有计划接种本试验用疫苗外的流感疫苗；
3. 入组前3个月内患有流感疾病（经临床、血清学或微生物学任一方法证实的）；
4. 对试验用疫苗的任何成分（包括：牛血清白蛋白、甲醛、TritonX-100等）、鸡蛋或鸡蛋蛋白有过严重过敏史，如过敏性休克、过敏性喉头水肿、过敏性紫癜、血小板减少性紫癜、局部过敏坏死反应（Arthus反应）；
5. 既往有任何疫苗或药物严重不良反应史，例如：需要医疗干预的过敏、荨麻疹、皮肤湿疹、呼吸困难、血管神经性水肿等；
6. 入组前3天内，患急性疾病或处于慢性病的急性发作期；
7. 入组前接种其他非活疫苗间隔少于7天，接种减毒活疫苗、新冠疫苗间隔少于14天；
8. 入组前3天内发热（腋温≥38.5℃），或入组前3天内正在使用解热镇痛药或抗过敏药物；
9. 入组前3个月内长期使用免疫抑制剂或其它免疫调节药物（定义为连续使用超过14天），如糖皮质激素剂量为≥0.5mg/kg/天（吸入性和局部糖皮质激素不受限制）；
10. 入组前6个月接受过血液或血液相关制品；
11. 患有可能干扰研究进行或完成的先天畸形或遗传性疾病（唐氏综合症、地中海贫血、先天性心脏病等）、急慢性传染病（结核、各型病毒性肝炎等）、先天性或获得性的免疫缺陷（HIV）等；
12. 患有可能干扰研究进行或完成的严重的疾病（包括：患有哮喘等呼吸道疾病或慢性支气管炎发作期间，药物无法控制的高血压（收缩压≥160mmHg和/或舒张压≥100mmHg，仅≥18岁人群）、心脏病、肾病、糖尿病（血糖控制不稳定，或药物无法控制血糖，或有糖尿病并发症）、自身免疫病、遗传性过敏体质、格林巴利综合症、感染性/过敏性皮肤疾病等）；
13. 存在肌内注射禁忌症，例如：已被诊断为患有血小板减少症、任何凝血障碍或接受抗凝血剂治疗等；
14. 有癫痫、脑病和精神病史或家族史，半年内有惊厥病史；
15. 无脾、功能性无脾，以及任何情况导致的无脾或脾切除；
16. 计划在研究结束前搬离本地或在预定研究访视期间长时间离开本地；
17. 正在参加另一项临床试验者，以及在临床试验期间计划参加其他临床试验者；
18. 研究者认为，志愿者存在任何可能干扰对研究目的评估的状况。

Exclusion criteria：

1. Abnormal laboratory test indicators before immunization, and the abnormality is clinically significant as determined by the clinician;
2. Influenza vaccines other than those used in the study were planned during the study period;
3. Influenza illness (confirmed by clinical, serological or microbiological methods) within 3 months before enrollment;
4. Severe allergic history to any component of test vaccine (including bovine serum albumin, formaldehyde, TritonX-100, etc.), egg or egg protein, such as anaphylactic shock, allergic laryngeal edema, allergic purpura, thrombocytopenic purpura, local anaphylaxis and necrosis reaction (Arthus reaction);
5. Past history of serious adverse reactions to any vaccine or drug, such as allergy, urticaria, skin eczema, dyspnea, angiopanginal edema requiring medical intervention;
6. Acute illness or acute onset of chronic disease within 3 days before enrollment;
7. Before enrollment, the interval between vaccination with other non-live vaccines was less than 7 days, and the interval between vaccination with live attenuated vaccines and COVID-19 vaccines was less than 14 days;
8. Had fever (axillary temperature >=38.5 degree) within 3 days before enrollment, or was using antipyretic analgesics or antiallergic drugs within 3 days before enrollment;
9. Long-term use of immunosuppressive agents or other immunomodulatory drugs (defined as continuous use for more than 14 days) within 3 months before enrollment, such as glucocorticoid dose >=0.5mg/kg/ day (inhaled and local glucocorticoids are not restricted);
10. Received blood or blood-related products 6 months before enrollment;
11. Congenital malformations or inherited diseases (Down syndrome, thalassemia, congenital heart disease, etc.), acute or chronic infectious diseases (tuberculosis, various viral hepatitis, etc.), congenital or acquired immunodeficiency (HIV), etc., that may interfere with the conduct or completion of the study;
12. Suffers from a serious medical condition that may interfere with the conduct or completion of the study (including: Medication uncontrolled hypertension (systolic blood pressure >=160mmHg and/or diastolic blood pressure >=100mmHg, only in people 18 years of age or older), heart disease, kidney disease, diabetes (unstable blood glucose control, or medication failure to control blood glucose, Or diabetic complications), autoimmune diseases, hereditary allergies, Guillain-Barre syndrome, infectious/allergic skin diseases, etc.);
13. There are contraindications to intramuscular injection, such as having been diagnosed with thrombocytopenia, any coagulation disorder or being treated with anticoagulants;
14. A history or family history of epilepsy, encephalopathy and mental illness, and a history of convulsions within six months;
15. Asplenia, functional asplenia, and asplenia or splenectomy resulting from any condition;
16. Plan to move out of town before the end of the study or for an extended period of time during the scheduled study visit;
17. Persons who are participating in another clinical trial and who plan to participate in other clinical trials during the clinical trial;
18. In the opinion of the investigator, the volunteers had any condition that might interfere with the evaluation of the study's purpose.

研究实施时间：

Study execute time：

从 From 2022-10-21 00:00:00至 To 2023-05-20 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2022-10-21 00:00:00 至 To 2023-05-20 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	160
Group：	Intervention Group	Sample size：	160
干预措施：	四价流感病毒裂解疫苗（MDCK细胞）	干预措施代码：
Intervention：	Tetravalent influenza virus split vaccine (MDCK cells)	Intervention code：

组别：	阳性对照组	样本量：	100
Group：	Positive control group	Sample size：	100
干预措施：	四价流感病毒裂解疫苗	干预措施代码：
Intervention：	Tetravalent influenza virus split vaccine	Intervention code：

组别：	安慰剂组	样本量：	60
Group：	Placebo group	Sample size：	60
干预措施：	安慰剂	干预措施代码：
Intervention：	Placebo	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	山东	市(区县)：	济南
Country：	China	Province：	Shandong	City：	Jinan
单位(医院)：	山东省疾病预防控制中心	单位级别：
Institution hospital：	Shandong Provincial Center for Disease Control and Prevention	Level of the institution：

测量指标：

Outcomes：

指标中文名：	不良事件/反应发生率	指标类型：	主要指标
Outcome：	Incidence rate of adverse events/reactions	Type：	Primary indicator
测量时间点：	0-28/30天	测量方法：
Measure time point of outcome：	0-28/30 days	Measure method：

指标中文名：	实验室检测指标异常发生率	指标类型：	主要指标
Outcome：	Abnormal rate of laboratory test indicators	Type：	Primary indicator
测量时间点：	接种后第4天	测量方法：
Measure time point of outcome：	Day 4 after vaccination	Measure method：

指标中文名：	严重不良事件发生率	指标类型：	主要指标
Outcome：	Incidence rate of serious adverse events	Type：	Primary indicator
测量时间点：	0-6个月	测量方法：
Measure time point of outcome：	0-6 months	Measure method：

指标中文名：	流感病毒各型抗体阳转率和抗体水平	指标类型：	次要指标
Outcome：	Positive conversion rate and antibody level(GMT) of influenza virus types	Type：	Secondary indicator
测量时间点：	全程接种后30天	测量方法：
Measure time point of outcome：	30 days after full vaccination	Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	血液	组织：
Sample Name：	Blood	Tissue：
人体标本去向	使用后保存	说明
Fate of sample：	Preservation after use	Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	3	岁 years
最大 Max age		岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

由统计方分别在两个阶段采用分层区组随机化的方法分别产生随机表，分层因素为年龄。

Randomization Procedure (please state who generates the random number sequence and by what method)：

The statistical company used stratified block randomization method in two stages to generate random tables respectively, and the stratified factor was age.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：
Blinding：

是否共享原始数据： IPD sharing	否No
共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：	不适用（请阅读网址首页注册指南共享原始数据的方式内容）
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	NA
数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：	采用EDC系统进行数据管理
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	EDC system is used for data management
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2022-10-27 15:14:23