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免疫原性和安全性随机、双盲、安慰剂对照的Ⅱ期临床试验
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注册号:

Registration number:

ChiCTR2100045107 

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:

预注册  

Registration Status:

Prospective 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免疫原性和安全性随机、双盲、安慰剂对照的Ⅱ期临床试验 

Public title:

A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial to Evaluate the Immunogenicity and Safety 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免疫原性和安全性随机、双盲、安慰剂对照的Ⅱ期临床试验 

Scientific title:

A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial to Evaluate the Immunogenicity and Safety 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-II 

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:

Wang Wei 

Study leader:

Xu Zhonghui 

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:

2021V002-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:

2021-03-10 

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:

金湾区创业北路38号

Institution
hospital:

Livzon Mabpharm Inc.

Address:

38 Chuangye Road North, 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:

II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不同剂量、不同免疫程序重组新型冠状病毒融合蛋白疫苗的免疫原性; 次要目的:评价18岁及以上健康受试者接种不同剂量、不同免疫程序重组新型冠状病毒融合蛋白疫苗的安全性。 

Objectives of Study:

Primary objective: To evaluate the immunogenicity of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) administrated as per different schedules and dosages in healthy adults; Secondary objective: To evaluate the safety of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) administrated as per different schedules and dosages in healthy adults. 

药物成份或治疗方案详述:

本研究为随机、双盲和安慰剂对照试验。 II期启动时间: 在完成I期成人组50μg剂量组所有受试者的首剂接种后7天安全性观察后,将召开DSMB会议,DSMB将建议是否可以启动II期临床试验中所有成人受试者的入组。 在完成I期老年组50μg剂量组所有受试者的首剂接种后7天安全性观察后,将召开DSMB会议,DSMB将建议是否可以启动II期临床试验中所有老年组受试者的入组。 根据Ⅰ期安全性结果选择合适剂量(暂定2剂组剂量10μg、25μg,暂定1剂组剂量为50μg)。2剂组成人和老人受试者各分别入组280例,其中10μg组120例、25μg组120例和安慰剂组40例;1剂组成人和老人受试者各分别入组160例,其中50μg组120例、安慰剂组40例;合计880例受试者。 老年人群将按60-69岁、70岁及以上人群进一步分层,将按一定比例先后入组。 疫苗接种和随访: 2剂组: 于第0天、第21天在上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。 1剂组: 于第0天在上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 

Description for medicine or protocol of treatment in detail:

Phase II clinical trial is randomized, double-blind, and placebo-controlled. Initiating time for Phase II clinical trial: After all the subjects of the 50-μg subgroup under the Youth group finish the 7-day first dose safety observation in the Phase I clinical trial, call a DSMB meeting; DSMB will give suggestion on whether to start Phase II trial on all subjects of the Youth group. After all the subjects of the 50-μg subgroup under the Elder group finish the 7-day first dose safety observation in the Phase I clinical trial, call a DSMB meeting; DSMB will give suggestion on whether to start Phase II trial on all subjects of the Elder group. A total of 880 subjects are included in Phase II clinical trial and divided into a Youth group and an Elder group. Appropriate doses will be decided based on the safety results from phase Ⅰ trial (10 μg, 25 μg for the group of two doses, and 50 μg for the group of one dose, determined tentatively). The two-dose subgroups of each group contain 280 subjects (120 for V-01 administration under the 10-μg subgroup, 120 for V-01 administration under the 25-μg subgroup, 40 for placebo administration); the one-dose subgroup of each group includes 160 subjects (120 for v-01 administration, 40 for placebo administration). The Elder group is further divided into 60-69 years group and >= 70 years group for age-based stratification analysis following a certain sequence at a ratio. Vaccination and follow-up: Two-dose groups: All the subjects are administrated V-01 or placebo on Days 0 and Day 21 at the deltoid muscle in the upper arm and tested for safety, tolerance and immunogenicity as per the schedule described in the study protocol. One-dose group: All the subjects are administrated V-01 or placebo on Day 0 at the deltoid muscle in the upper arm and tested for safety, tolerance and immunogenicity as per the schedule described in the study protocol.  

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.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。 4.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。 5.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. 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; 4. 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; 5. 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.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; 7.签署知情同意前1年内有药物滥用/依赖史或毒品史者; 8.既往有酗酒史; 9.现患药物无法控制的严重慢性疾病(适用于≥60岁人群):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); 10.先天或获得性的血管性水肿/神经性水肿病史; 11.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; 12.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; 13.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; 14.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); 15.已接受SARS-CoV-2疫苗紧急使用或接种上市后新冠疫苗; 16.已被诊断为患有先天性或获得性的免疫缺陷、或怀疑患有可能干扰研究进行或完成的全身性疾病,例如:结核、病毒性肝炎、人类免疫性缺陷病毒(HIV)感染、梅毒感染等; 17.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; 18.免疫前3个月内使用免疫球蛋白和/或任何血液制品; 19.免疫前6个月内接受过其他研究药物; 20.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. 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; 7. History of drug abuse/dependence within 1 year prior to signing the informed consent; 8. Past history of alcoholism; 9. 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); 10. History of congenital or acquired angioneurotic edema; 11. 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); 12. History of autoimmune diseases, excluding mild psoriasis, controllable autoimmune thyroid disease, vitiligo, or stable celiac disease that does not require immunosuppressive or immunomodulatory therapy; 13. Pregnant women or women expected to get pregnant within 12 months after the last dose and breastfeeding women; 14. At high risk of SARS-CoV-2 exposure (such as medical staff, health care providers in direct contact with patients); 15. Having received SARS-CoV-2 vaccines for emergency use or approved SARS-CoV-2 vaccines; 16. Having been diagnosed with congenital or acquired immunodeficiency, or suspected of systemic diseases that may interfere with the progress or completion of the study, such as tuberculosis, viral hepatitis, human immunodeficiency virus (HIV) infection, syphilis infection, etc.; 17. 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; 18. Administration of immunoglobulins and/or any blood products within 3 months prior to the investigational vaccine dose; 19. Administration of other investigational drugs within 6 months prior to the investigational vaccine dose; 2O. 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:

From2021-03-28To 2022-07-30 

征募观察对象时间:

Recruiting time:

From2021-03-28To 2021-05-30 

干预措施:

Interventions:

组别:

X组:10μg成人组(18-59岁)和25μg成人组(18-59岁)

样本量:

280

Group:

Group X: Two-dose 10-ug youth (18-59 years) group and two-dose 25-ug youth (18-59 years) group

Sample size:

干预措施:

于第0天、第21天在上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。

干预措施代码:

Intervention:

All the subjects are administrated V-01 or placebo on Days 0 and Day 21 at the deltoid muscle in the upper arm and tested for safety, tolerance and immunogenicity as per the schedule described in the study protocol.

Intervention code:

组别:

Y组:10μg老人组(≥60岁)和25μg老人组(≥60岁)

样本量:

280

Group:

Group Y: Two-dose 10-ug elder (>=60 years) group and two-dose 25-ug elder (>=60 years) group

Sample size:

干预措施:

于第0天、第21天在上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。

干预措施代码:

Intervention:

All the subjects are administrated V-01 or placebo on Days 0 and Day 21 at the deltoid muscle in the upper arm and tested for safety, tolerance and immunogenicity as per the schedule described in the study protocol.

Intervention code:

组别:

Z组:50μg成人组(18-59岁)

样本量:

160

Group:

Group Z: One-dose 50-ug youth (18-59 years) group

Sample size:

干预措施:

于第0天在上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。

干预措施代码:

Intervention:

All the subjects are administrated V-01 or placebo on Day 0 and at the deltoid muscle in the upper arm and tested for safety, tolerance and immunogenicity as per the schedule described in the study protocol.

Intervention code:

组别:

W组:50μg老人组(≥60岁)

样本量:

160

Group:

Group W: One-dose 50-ug elder (>=60 years) group

Sample size:

干预措施:

于第0天在上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。

干预措施代码:

Intervention:

All the subjects are administrated V-01 or placebo on Day 0 at the deltoid muscle in the upper arm and tested for safety, tolerance and immunogenicity as per the schedule described in the study protocol.

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:

1.血清抗SARS-CoV-2 RBD蛋白结合抗体阳转率、几何平均滴度(Geometric Mean Titer,GMT)、几何平均增长倍数(Geometric Mean Fold Increase,GMI)(酶联免疫吸附测定法(Enzyme-linked Immuno Sorbent Assay,ELISA);2. 血清抗SARS-CoV-2中和抗体阳转率、GMT、GMI

指标类型:

主要指标 

Outcome:

1.Positive conversion rate of serum anti-SARS-CoV-2 RBD protein antibody, and its geometric mean titer (GMT) and geometric mean fold increase (GMI); 2. Positive conversion rate of serum anti-SARS-CoV-2 neutralizing antibody, and its GMI

Type:

Primary indicator 

测量时间点:

on 28 days after the last dose

测量方法:

by Enzyme-linked Immuno Sorbent Assay (ELISA) and(活病毒、假病毒中和试验法)

Measure time point of outcome:

on 28 days after the last dose

Measure method:

by Enzyme-linked Immuno Sorbent Assay (ELISA) and Neutralization test for live virus and pseudo virus

指标中文名:

安全性指标

指标类型:

次要指标 

Outcome:

Safety outcomes

Type:

Secondary 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

指标类型:

次要指标 

Outcome:

Immunogenicity outcomes

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 100 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):

由随机化统计师采用SAS (9.4及以上版本),对2剂程序组和1剂程序组分别采用分层区组随机化方法(按照年龄组进行分层:18-59岁 vs ≥60岁)产生随机表。其中,2剂程序组每个年龄组内受试者按照入组顺序以3:3:1的比例被随机分配至10μg疫苗组、25μg疫苗组或安慰剂组,1剂程序组每个年龄组内受试者按照入组顺序以3:1的比例被随机分配至50μg疫苗组或安慰剂组。

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

For the planned 2-dose and 1-dose youth (18-59 years) and elder (>=60 years) groups, block randomization is performed by the randomization statistician using SAS (Version 9.4 and above). Specifically, based on the chronological sequence of enrollment.

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):

未说明 请阅读网页注册指南中关于“原始数据共享”的内容。

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

Not stated

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
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