今天是:2021-11-30 星期二

评价重组新型冠状病毒融合蛋白疫苗在健康人群安全性和免疫原性随机、双盲、安慰剂对照的Ⅰ期临床试验
下载XML文档

注册号:

Registration number:

ChiCTR2100045108 

最近更新日期:

Date of Last Refreshed on:

2021-11-08 

注册时间:

Date of Registration:

2021-04-07 

注册号状态:

补注册  

Registration Status:

Retrospective registration  

注册题目:

评价重组新型冠状病毒融合蛋白疫苗在健康人群安全性和免疫原性随机、双盲、安慰剂对照的Ⅰ期临床试验 

Public title:

A Randomized, Double-Blind, Placebo-Controlled Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) in Healthy Subjects 

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

评价重组新型冠状病毒融合蛋白疫苗在健康人群安全性和免疫原性随机、双盲、安慰剂对照的Ⅰ期临床试验 

Scientific title:

A Randomized, Double-Blind, Placebo-Controlled Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) in Healthy Subjects 

研究课题代号(代码):

Study subject ID:

V-01-I 

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:

王维 

研究负责人:

徐忠辉 

Applicant:

Wei Wang 

Study leader:

Zhonghui Xu 

申请注册联系人电话:

Applicant telephone:

+86 18515960943 

研究负责人电话:

Study leader's telephone:

+86 18627028600 

申请注册联系人传真 :

Applicant Fax:

 

研究负责人传真:

Study leader's fax:

 

申请注册联系人电子邮件:

Applicant E-mail:

wangwei17@livzon.cn 

研究负责人电子邮件:

Study leader's E-mail:

xuzhonghui@livzon.cn 

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:

广东省珠海市金湾区创业北路38号单抗大楼 

研究负责人通讯地址:

广东省珠海市金湾区创业北路38号单抗大楼 

Applicant address:

38 Chuangye Road North, Jinwan District, Zhuhai, Guangdong, China 

Study leader's address:

38 Chuangye Road North, Jinwan District, Zhuhai, Guangdong, China 

申请注册联系人邮政编码:

Applicant postcode:

519000 

研究负责人邮政编码:

Study leader's postcode:

519000 

申请人所在单位:

珠海市丽珠单抗生物技术有限公司 

Applicant's institution:

Livzon Mabpharm Inc. 

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:

2021V001-F 

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:

广东省疾病预防控制中心疫苗临床研究伦理审查委员会 

Name of the ethic committee:

The Ethics Committee for Clinical Trials of Vaccines, Guangdong Provincial Center for Disease Control and Prevention 

伦理委员会批准日期:

Date of approved by ethic committee:

2021-02-07 

伦理委员会联系人:

陈诗颖 

Contact Name of the ethic committee:

Shiying Chen 

伦理委员会联系地址:

广东省广州市白云区鹤龙街细彭岭路12号 

Contact Address of the ethic committee:

12 Xipengling Road, Helong Street, Baiyun District, Guangzhou, Guangdong, China 

伦理委员会联系人电话:

Contact phone of the ethic committee:

+86 20 89024059 

伦理委员会联系人邮箱:

Contact email of the ethic committee:

vctiec@cdcp.org.cn 

研究实施负责(组长)单位:

广东省疾病预防控制中心/高州市疾病预防控制中心 

Primary sponsor:

Guangdong Provincial Center for Disease Control and Prevention/ Gaozhou Municipal Center for Disease Control and Prevention 

研究实施负责(组长)单位地址:

广东省广州市番禺区大石街群贤路160号/广东省茂名市高州市桂圆路38号 

Primary sponsor's address:

160 Qunxian Road, Dashi Street, Panyu District, Guangzhou, Guangdong; 38 Guiyuan Road, Gaozhou, Maoming, Guangdong, China 

试验主办单位(项目批准或申办者):

Secondary sponsor:

国家:

中国

省(直辖市):

广东

市(区县):

珠海

Country:

China

Province:

Guangdong

City:

Zhuhai

单位(医院):

珠海市丽珠单抗生物技术有限公司

具体地址:

珠海市金湾区创业北路38号

Institution
hospital:

Livzon Mabpharm Inc.

Address:

38 Chuangye North Road, Jinwan District

经费或物资来源:

珠海市丽珠单抗生物技术有限公司 

Source(s) of funding:

Livzon Mabpharm Inc. 

研究疾病:

新型冠状病毒肺炎(COVID-19) 

Target disease:

Novel Coronavirus Pneumonia (COVID-19)  

研究疾病代码:

 

Target disease code:

 

研究类型:

预防性研究 

Study type:

Prevention 

研究所处阶段:

I期临床试验 

Study phase:

研究目的:

主要目的:评价18岁及以上健康受试者接种重组新型冠状病毒融合蛋白疫苗的安全性和耐受性; 次要目的:初步评价18岁及以上健康受试者接种重组新型冠状病毒融合蛋白疫苗的免疫原性。 

Objectives of Study:

Primary objective: To evaluate the safety and tolerance of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) in healthy adults; Secondary objective: To preliminarily evaluate the immunogenicity of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) in healthy adults. 

药物成份或治疗方案详述:

本研究为单中心、随机、双盲和安慰剂对照试验。 采用剂量爬坡设计,包含10μg、25μg和50μg三个剂量组,计划共入组180例18岁及以上健康受试者(男性或女性)。其中,成人组90例,每个剂量组30例;老年组90例,每个剂量组30例。每个剂量组内受试者按4:1比例随机分配至试验组或安慰剂对照组。 为保障受试者安全性,将按照从低剂量组到高剂量组、成年人到老年人的顺序开展,由研究者/DSMB评估安全性结果,决定是否继续下一组别入组/启动Ⅱ期临床试验: 哨兵安全性观察: 每个剂量组年龄分组先入组5名哨兵,全部哨兵完成首剂免后至少4天的安全性观察(包括实验室安全性检查),经研究者判定安全(未达到暂停终止标准),开放该剂量组年龄分组内的其余受试者入组。此外,所有哨兵在首剂接种后7天,确认安全(未出现符合暂停/终止标准的安全性事件)后,后续才可进行第2针免疫接种。 哨兵剂量爬坡: 完成上一剂量/年龄分组5名哨兵首剂免后7天安全性观察后,经研究者判定安全(未达到暂停终止标准),可开放下一剂量/年龄分组哨兵入组。 其余受试者剂量爬坡: 完成上一剂量/年龄分组其余受试者首剂免后7天安全性观察,且完成本剂量/年龄分组哨兵受试者首剂免后4天安全性观察后,经研究者判定安全(未达到暂停终止标准),可开放本剂量/年龄分组其余受试者入组。 依次类推,完成全部剂量组入组和观察。 疫苗接种和随访: 于第0天、第21天在手臂三角肌肌肉注射试验疫苗或安慰剂。按照方案规定的时间计划进行安全性、耐受性及免疫原性相关检查(详细流程见研究流程表)。 

Description for medicine or protocol of treatment in detail:

The study is a single-center, randomized, double-blind and placebo-controlled clinical trial. As a dose-escalating study, it is planned to include 180 healthy adults (male and female) and divide them into the Youth group (n=90) and the Elder group (n=90) according to their ages; each age group has three subgroups, i.e. 10-μg subgroup (n= 30), 25-μg subgroup (n= 30) and 50-μg subgroup (n= 30), which are further divided for V-01 administration (test subgroup) and placebo administration (control group) at a ratio of 4:1 (V-01 : placebo). To ensure the safety of the subjects, the study protocol is carried out in a sequence of from low dose to high dose and from the youth to the elder. Based on the safety observation by the Investigator/DSMB, the study proceeds to a higher dose/an elder age or the Phase II trial or not. Sentinel-based safety observation For each dose subgroup, 5 sentinels are arranged. After the first dose, the 5 sentinels are subjected to safety observation (including the safety tests in labs) for at least 4 days. If the Investigator decides that the 5 sentinels are safe (against the discontinuation/termination criteria), other subjects for the same dose subgroup will be included for study. Besides, the 5 sentinels can have the second dose only when they are evaluated as safe against the discontinuation/termination criteria 7 days after the first dose. Dose escalating with sentinels When the 5 sentinels of a subgroup evaluated as safe against the discontinuation/termination criteria by the Investigator after the 7-day first-dose safety observation, the study could move on to 5 sentinels for the next higher dose/elder subgroup. Dose escalating with subjects other than sentinels When other subjects other than the 5 sentinels of a subgroup evaluated as safe against the discontinuation/termination criteria by the Investigator after the 4-day first-dose safety observation of the 5 sentinels and then 7-day first-dose safety observation of the other subjects, the study could move on to other subjects for the next higher dose/elder subgroup. Repeat the above dose escalating steps until all the dose subgroups finish the inclusion and observation. Vaccination and follow-up: All the subjects are administrated V-01 or placebo on Days 0 and Day 21 at the deltoid muscle in the arm and tested for safety, tolerance and immunogenicity as per the schedule described in the study protocol (detailed in the study flow chart). 

研究设计:

随机平行对照 

Study design:

Parallel 

纳入标准:

满足以下所有标准的受试者可考虑入组: 1.自愿参加研究,并签署知情同意。 2.男性或女性健康受试者,18岁及以上(含下限临界值)。 3.体重指数在18~28kg/m2范围内(含临界值)。 4.过去14天内无疫情高、中风险区、境外及出现过疫情地区旅行史或居住史;且过去14天内无新型冠状病毒感染确诊病例、无症状感染者或疑似病例接触史;且过去14天内无来自疫情高、中风险区发热或有呼吸道症状患者接触史;且处于非隔离期内人员,生活地区无聚集性发病。 5.具有生育能力的男性和育龄期女性愿意从签署知情同意书开始至试验疫苗末次接种后12个月内采取有效避孕措施;育龄期女性包括绝经前女性和绝经后2年内的女性。育龄期女性在试验疫苗首次免疫前≤7天内的妊娠检测结果必须为阴性。 6.自愿受试并遵守试验方案要求,能配合完成规定的各项检查。 

Inclusion criteria

Subjects who comply with the following criteria will be enrolled: 1. Willing to participate in the study with informed consent; 2. Health male or female adults (i.e. aged 18 years and above); 3. BMI within 18-28 kg/m2 (including both boundaries); 4. Without a history of traveling or residence in domestic areas of high and moderate pandemic risk, overseas or epidemic areas, nor a history of contact with confirmed, asymptomatic or suspected COVID-19 cases, or patients coming from areas of high and moderate pandemic risk who have fever or respiratory tract symptoms within the past 14 days; being not in quarantine and not living in an area with cluster of COVID-19 cases; 5. Males with fertility and women of childbearing potential who are willing to take effective contraceptive measures during the period from the date of signing the informed consent to 12 months after the last dose of the investigational vaccines; women of childbearing potential refer to premenopausal women and women within 2 years after menopause. Women of childbearing potential should test negative for pregnancy within 7 days prior to the first dose of the investigational vaccines; 6. Willing to abide by the study protocol by cooperatively receiving required examinations. 

排除标准:

符合以下任何一条标准的受试者不可入组: 1.新型冠状病毒感染确诊病例或无症状感染者; 2.新型冠状病毒核酸检测阳性; 3.新型冠状病毒抗体IgG或IgM阳性(必要时结合核酸检测和胸部CT检查进行确认是否需排除); 4.SARS病毒患病史; 5.签署知情同意前14天内出现发热(腋温≥37.3℃)等急性疾病或慢性疾病急性发作者; 6.筛选期检测血生化、血常规、尿常规、凝血功能、抗核抗体相关指标有临床意义的异常者; 7.既往发生过疫苗接种严重过敏反应(如急性过敏反应、荨麻疹、皮肤湿疹、呼吸困难、血管神经性水肿或腹痛)或对新型冠状病毒疫苗已知成份过敏; 8.签署知情同意前1年内有药物滥用/依赖史或毒品史者; 9.既往有酗酒史。 10.现患药物无法控制的严重慢性疾病(适用于≥60岁):慢性呼吸系统疾病史(包括中至重度哮喘、COPD、肺纤维化)、药物无法控制的高血压(收缩压≥140mmHg和/或舒张压≥90mmHg)、严重心血管疾病病史(包括心力衰竭、冠状动脉疾病、心肌病)、慢性肾脏疾病史、癌症史、糖尿病(血糖控制不理想或有糖尿病相关的严重并发症); 11.先天或获得性的血管性水肿/神经性水肿病史; 12.任何已确认或怀疑的免疫抑制或免疫缺陷状态,包括艾滋病毒感染、无脾;在过去的6个月内,复发性严重感染和使用免疫抑制剂药物,局部类固醇或短期口服类固醇(疗程<14天)除外; 13.任何自身免疫疾病史,轻度牛皮癣、可控的自身免疫性甲状腺疾病、白癜风或不需要免疫抑制剂或免疫调节疗法治疗的稳定的乳糜泻除外; 14.妊娠期女性或全程免后12个月内有妊娠计划的女性或其伴侣以及哺乳期女性; 15.SARS-CoV-2暴露高风险者(如:医护人员、与患者直接接触的卫生保健工作者); 16.已接受SARS-CoV-2疫苗紧急使用或接种上市后SARS-CoV-2疫苗; 17.感染筛查(丙型肝炎病毒抗体、梅毒螺旋体抗体检查或人类免疫缺陷病毒抗体检查)结果呈阳性者; 18.免疫前1个月内免疫过减毒活疫苗或免疫前14天内免疫过其他疫苗; 19.免疫前3个月内使用免疫球蛋白和/或任何血液制品; 20.免疫前6个月内接受过其他研究药物; 21.根据研究者判断,由于各种医疗、心理、社会条件或其他条件,有悖于试验方案,或影响受试者签署知情同意的。 

Exclusion criteria:

Subjects who meet any of the following criteria will be excluded: 1. Confirmed or asymptomatic COVID-19 cases; 2. Positive SARS-CoV-2 nucleic acid test; 3. Positive SARS-CoV-2 IgG or IgM test (reference to nucleic acid test and chest CT if necessary); 4. History of SARS; 5. Fever (axillary temperature >= 37.3 degrees C) or other acute diseases, or in the acute phase of chronic diseases within 14 days prior to the signing of the informed consent form; 6. With significantly abnormal laboratory test results during screening, including biochemical profile, hematology, urinalysis, coagulation function and antinuclear antibody; 7. Past history of allergies to vaccines (e.g., acute allergic reactions, hives, skin eczema, dyspnea, angioneurotic edema, or abdominal pain), or allergic to any known ingredients of COVID-19 vaccines; 8. History of drug abuse/dependence within 1 year prior to signing the informed consent; 9. Past history of alcoholism; 10. Having severe chronic diseases that cannot be controlled by drugs (individuals >= 60 years): chronic respiratory diseases (including moderate to severe asthma, COPD, pulmonary fibrosis), uncontrolled hypertension (systolic blood pressure >=140 mmHg and/or diastolic blood pressure >= 90 mmHg), severe cardiovascular diseases (including cardiac failure, coronary artery disease, cardiomyopathy), chronic kidney disease, cancer, diabetes (unacceptable glycemia control or serious diabetic complications); 11. History of congenital or acquired angioneurotic edema; 12. Any confirmed or suspected immunosuppressive or immunodeficiency disorder, including HIV infection and asplenia; recurrent severe infections and administration of immunosuppressive drugs during the past 6 months, excluding topical steroids or short-term oral steroids (< 14 days); 13. History of autoimmune diseases, excluding mild psoriasis, controllable autoimmune thyroid disease, vitiligo, or stable celiac disease that does not require immunosuppressive or immunomodulatory therapy; 14. Pregnant women or women expected to get pregnant within 12 months after the last dose and breastfeeding women; 15. At high risk of SARS-CoV-2 exposure (such as medical staff, health care providers in direct contact with patients); 16. Having received SARS-CoV-2 vaccines for emergency use or approved SARS-CoV-2 vaccines; 17. Positive screening test results (Hepatitis C virus antibody, treponema pallidum antibody, HIV antibody); 18. Administration of a live attenuated vaccine within 1 month prior to the investigational vaccine dose, or other vaccines within 14 days prior to the investigational vaccine dose; 19. Administration of immunoglobulins and/or any blood products within 3 months prior to the investigational vaccine dose; 20. Administration of other investigational drugs within 6 months prior to the investigational vaccine dose; 21. Other scenarios that may be medically, psychologically or socially contradicted with the study protocol at the investigators discretion or preclude informed consents of the subjects. 

研究实施时间:

Study execute time:

From2021-02-22To 2022-06-30 

征募观察对象时间:

Recruiting time:

From2021-02-22To 2021-03-25 

干预措施:

Interventions:

组别:

A组:10μg成人组(18-59岁)

样本量:

30

Group:

Group A: 10-ug youth (18-59 years) group

Sample size:

干预措施:

所有受试者在第0、21天分别接种重组新型冠状病毒融合蛋白疫苗或安慰剂一次。

干预措施代码:

Intervention:

All subjects are given one dose of V-01 or placebo on Days 0 and 21.

Intervention code:

组别:

B组:25μg成人组(18-59岁)

样本量:

30

Group:

Group B: 25-ug youth (18-59 years) group

Sample size:

干预措施:

所有受试者在第0、21天分别接种重组新型冠状病毒融合蛋白疫苗或安慰剂一次。

干预措施代码:

Intervention:

All subjects are given one dose of V-01 or placebo on Days 0 and 21.

Intervention code:

组别:

C组:50μg成人组(18-59岁)

样本量:

30

Group:

Group C: 50-ug youth (18-59 years) group

Sample size:

干预措施:

所有受试者在第0、21天分别接种重组新型冠状病毒融合蛋白疫苗或安慰剂一次。

干预措施代码:

Intervention:

All subjects are given one dose of V-01 or placebo on Days 0 and 21.

Intervention code:

组别:

D组:10μg老年组(≥60岁)

样本量:

30

Group:

Group D: 10-ug elder (>=60 years) group

Sample size:

干预措施:

所有受试者在第0、21天分别接种重组新型冠状病毒融合蛋白疫苗或安慰剂一次。

干预措施代码:

Intervention:

All subjects are given one dose of V-01 or placebo on Days 0 and 21.

Intervention code:

组别:

E组:25μg老年组(≥60岁)

样本量:

30

Group:

Group E: 25-ug elder (>=60 years) group

Sample size:

干预措施:

所有受试者在第0、21天分别接种重组新型冠状病毒融合蛋白疫苗或安慰剂一次。

干预措施代码:

Intervention:

All subjects are given one dose of V-01 or placebo on Days 0 and 21.

Intervention code:

组别:

F组:50μg老年组(≥60岁)

样本量:

30

Group:

Group F: 50-ug elder (>=60 years) group

Sample size:

干预措施:

所有受试者在第0、21天分别接种重组新型冠状病毒融合蛋白疫苗或安慰剂一次。

干预措施代码:

Intervention:

All subjects are given one dose of V-01 or placebo on Days 0 and 21.

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

广东 

市(区县):

高州 

Country:

China 

Province:

Guangdong 

City:

Gaozhou 

单位(医院):

高州市疾病预防控制中心 

单位级别:

 

Institution
hospital:

Gaozhou Municipal Center for Disease Control and Prevention  

Level of the institution:

 

测量指标:

Outcomes:

指标中文名:

安全性

指标类型:

主要指标 

Outcome:

Safety

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

免疫原性

指标类型:

次要指标 

Outcome:

Immunogenicity

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

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

其它 

说明

Fate of sample:

Others 

Note:

征募研究对象情况:

Recruiting status:

正在进行

Recruiting

年龄范围:

Participant age:

最小 Min age 18 years
最大 Max age / 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):

本研究采用剂量递增设计,计划成人组和老年组三个剂量组(10μg、25μg、50μg)各入组30例受试者,按4:1比例随机分配至试验组或安慰剂组。 由随机化统计师采用SAS (9.4及以上版本),对不同年龄组(按成人组和老年组)和不同剂量组(10μg、25μg、50μg)分别采用区组随机化方法产生随机表,按4:1的比例随机分配至疫苗组或安慰剂组。

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

As a dose-escalating study, it is planned to adopt six groups according to age (youth and elder) and dosage (10 ug, 25ug and 50ug), n= 30 in each group; each group is further divided for V-01 administration (test group) and placebo administration (control group) at a ratio of 4:1 (V-01: placebo).

盲法:

双盲

Blinding:

Double blind

试验完成后的统计结果(上传文件):

Calculated Results after
the Study Completed(upload file):

是否共享原始数据:

IPD sharing

是Yes

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):

研究总结报告方式

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url):

Using a final study report

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:

采用电子采集和管理系统

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture:

Using an electronic data capture system.

数据与安全监察委员会:

Data and Safety Monitoring Committee:

有/Yes

注册人:

Name of Registration:

 2021-04-07
返回列表