ChiCTR2100053747 版本V1.3 版本创建时间2023/09/14 09:35:01 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

ChiCTR2100053747 

最近更新日期：

Date of Last Refreshed on：

2023-09-13 18:04:44 

注册时间：

Date of Registration：

2021-11-28 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

Development of a COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores Expressing and Displaying the Receptor Binding Domain of Spike Protein of SARS-COV2

Public title：

Development of a COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores Expressing and Displaying the Receptor Binding Domain of Spike Protein of SARS-COV2

注册题目简写：

English Acronym：

研究课题的正式科学名称：

Expression of SARS-COV2 Spike Protein Receptor Binding Domain on Recombinant Bacillus subtilis on Spore Surface

Scientific title：

Expression of SARS-COV2 Spike Protein Receptor Binding Domain on Recombinant Bacillus subtilis on Spore Surface

研究课题代号(代码)：

Study subject ID：

 PRP/008/21FX

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：

Kwong Wai Yeung 

研究负责人：

Kwong Wai Yeung 

Applicant：

Kwong Wai Yeung 

Study leader：

Kwong Wai Yeung 

申请注册联系人电话：

Applicant telephone：

+852 95184614

研究负责人电话：

Study leader's telephone：

+852 95184614

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：

keithkwong@dreamtec.hk

研究负责人电子邮件：

Study leader's E-mail：

keithkwong@dreamtec.hk

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

Dreamtec Limited

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：

Unit G, 12/F City Ind Complex 71 - 77 Yau Ma Hom Rd, Kwai Chung, Hong Kong, China

研究负责人通讯地址：

Unit G, 12/F City Ind Complex 71 - 77 Yau Ma Hom Rd, Kwai Chung, Hong Kong, China3

Applicant address：

Unit G, 12/F City Ind Complex 71 - 77 Yau Ma Hom Rd, Kwai Chung, Hong Kong, China

Study leader's address：

Unit G, 12/F City Ind Complex 71 - 77 Yau Ma Hom Rd, Kwai Chung, Hong Kong

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：

香港Dreamtec Limited

Applicant's institution：

Dreamtec Limited

研究负责人所在单位：

香港Dreamtec Limited

Affiliation of the Leader：

Dreamtec Limited

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

DTREA010321

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：

Ethic Committees of Doctors Think Tank Academy

Name of the ethic committee：

Ethic Committees of Doctors Think Tank Academy

伦理委员会批准日期：

Date of approved by ethic committee：

2021-03-21 00:00:00

伦理委员会联系人：

Dr. Sunny Wong

Contact Name of the ethic committee：

Dr. Sunny Wong

伦理委员会联系地址：

Room 606 Hollywood Centre, 77-91 Queen's road west, Hong Kong, China

Contact Address of the ethic committee：

Room 606 Hollywood Centre, 77-91 Queen's road west, Hong Kong, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+852 68468772

伦理委员会联系人邮箱：

Contact email of the ethic committee：

admin@dttac.com

研究实施负责（组长）单位：

DreamTec Limited

Primary sponsor：

DreamTec Limited

研究实施负责（组长）单位地址：

Unit G, 12/F City Ind Complex 71 - 77 Yau Ma Hom Rd, Kwai Chung, Hong Kong, China

Primary sponsor's address：

Unit G, 12/F City Ind Complex 71 - 77 Yau Ma Hom Rd, Kwai Chung, Hong Kong, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

省(直辖市)：

市(区县)：

Country：

Province：

City：

单位(医院)：

具体地址：

Institution
hospital：

Address：

经费或物资来源：

DreamTec Limited

Source(s) of funding：

DreamTec Limited

Target disease：

novel coronavirus pneumonia

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 探索性研究/预试验 

Study phase：

0

研究设计：

单臂 

Study design：

Single arm 

研究目的：

Bacillus subtilis is regarded as safe organism by The Food and Drug Administration and it is presented in most food sources. Preliminary experiments have shown that the genetically engineered Bacillus subtilis can express and display receptor binding domain of spike protein of the SARS-COV2 on its spore coat, thus successfully induce the secretion of cytokines of human cells in vitro. Previous experiments also successfully demonstrated that a increased detection of neutralizing IgG and igM levels in mice after oral administrated with the Bacillus subtilis. This suggests that the transgenic spores of Bacillus subtilis have successfully activated the immune system, producing high-affinity neutralizing antibodies and memory B cells. Furthermore, no adverse effects were shown in all the mices. The engineered Bacillus subtilis will be further studied in a human trials through oral administration to test its safety and the immune effect resulted in human bodys.  

Objectives of Study：

Bacillus subtilis is regarded as safe organism by The Food and Drug Administration and it is presented in most food sources. Preliminary experiments have shown that the genetically engineered Bacillus subtilis can express and display receptor binding domain of spike protein of the SARS-COV2 on its spore coat, thus successfully induce the secretion of cytokines of human cells in vitro. Previous experiments also successfully demonstrated that a increased detection of neutralizing IgG and igM levels in mice after oral administrated with the Bacillus subtilis. This suggests that the transgenic spores of Bacillus subtilis have successfully activated the immune system, producing high-affinity neutralizing antibodies and memory B cells. Furthermore, no adverse effects were shown in all the mices. The engineered Bacillus subtilis will be further studied in a human trials through oral administration to test its safety and the immune effect resulted in human bodys.

药物成份或治疗方案详述：

Bacillus subtilis, a harmless intestinal commensal, has earned in recent years, great reputation as a vaccine production host and delivery vector with advantages such as low cost, safe for human consumption and straightforward administration. The technology team has succeeded engineering Bacillus subtilis with spore coat proteins resembling the proteins of the nucleus and spikes of coronal virus. This product could have a vaccine like activity within the intestinal environment. participants received vaccine 1 capsule of 1 x 10^10 CFU of B. subtilis spore at day 0, 14, and 28 respectively. To assess the safety of the engineered Bacillus subtilis [ Time Frame: 3 months ] Measure the weight changes in kilograms and number of incidence of adverse event from the beginning of the vaccination to 20 days after the third dose. Serum Neutralizing receptor binding domain IgG antibody concentration [ Time Frame: 3 months ] Concentration of neutralizing IgG antibody against receptor binding domain of spike protein in SARS-COV2. 

Description for medicine or protocol of treatment in detail：

Bacillus subtilis, a harmless intestinal commensal, has earned in recent years, great reputation as a vaccine production host and delivery vector with advantages such as low cost, safe for human consumption and straightforward administration. The technology team has succeeded engineering Bacillus subtilis with spore coat proteins resembling the proteins of the nucleus and spikes of coronal virus. This product could have a vaccine like activity within the intestinal environment. participants received vaccine 1 capsule of 1 x 10^10 CFU of B. subtilis spore at day 0, 14, and 28 respectively. To assess the safety of the engineered Bacillus subtilis [ Time Frame: 3 months ] Measure the weight changes in kilograms and number of incidence of adverse event from the beginning of the vaccination to 20 days after the third dose. Serum Neutralizing receptor binding domain IgG antibody concentration [ Time Frame: 3 months ] Concentration of neutralizing IgG antibody against receptor binding domain of spike protein in SARS-COV2. 

纳入标准：

1. healthy;
2. age over 25 years;
3. the outcome of the following examinations should be clinically insignificant: medical and surgical history (hypo-, hypertension, allergy, other diseases, major surgery, micturition, defecation, sleep, illness within the last 4 weeks prior to the start of the trial);
4. participant vaccinated with Sinovac over 4 months;
5. anti-SARS CoV 2 neutralizing antibody is negative in serum.

Inclusion criteria

1. healthy;
2. age over 25 years;
3. the outcome of the following examinations should be clinically insignificant: medical and surgical history (hypo-, hypertension, allergy, other diseases, major surgery, micturition, defecation, sleep, illness within the last 4 weeks prior to the start of the trial);
4. participant vaccinated with Sinovac over 4 months;
5. anti-SARS CoV 2 neutralizing antibody is negative in serum.

排除标准：

1. pregnant women;
2. history of COVID-19 infection or showing COVID-19 infection symptoms;
3. having had contact to people with known COVID-19 infection in the last 14 days;
4. having fever (> 37.4oC in the last 24 hours), dry cough or feeling tired and having aches and pains, nasal congestion, runny nose, sore throat and diarrhea;
5. positive real time RT-PCR COVID-19 test;
6. persons with autoimmune diseases;
7. allergic diathesis or any clinically significant allergic disease (i.e. asthma);
8. any condition that might impair the immune response;
9. recent or current immunosuppressive medication;
10. any other vaccine application 30 days before the first dose.

Exclusion criteria：

1. pregnant women;
2. history of COVID-19 infection or showing COVID-19 infection symptoms;
3. having had contact to people with known COVID-19 infection in the last 14 days;
4. having fever (> 37.4oC in the last 24 hours), dry cough or feeling tired and having aches and pains, nasal congestion, runny nose, sore throat and diarrhea;
5. positive real time RT-PCR COVID-19 test;
6. persons with autoimmune diseases;
7. allergic diathesis or any clinically significant allergic disease (i.e. asthma);
8. any condition that might impair the immune response;
9. recent or current immunosuppressive medication;
10. any other vaccine application 30 days before the first dose.

研究实施时间：

Study execute time：

从 From 2021-04-01 00:00:00至 To 2022-03-01 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2021-04-01 00:00:00 至 To 2021-12-01 00:00:00  

干预措施：

Interventions：

组别：

Case series

样本量：

30

Group：

Case series

Sample size：

干预措施：

Bacillus subtilis spore

干预措施代码：

Intervention：

Bacillus subtilis spore

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

省(直辖市)：

  

市(区县)：

  

Country：

 

Province：

 

City：

 

单位(医院)：

 

单位级别：

 

Institution
hospital：

Level of the institution：

测量指标：

Outcomes：

指标中文名：

Weight

指标类型：

主要指标

Outcome：

Weight

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

Neutralizing antibody level

指标类型：

次要指标

Outcome：

Neutralizing antibody level

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：

Blood

组织：

Vein

Sample Name：

Blood

Tissue：

Vein

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

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 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）：

N/A

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

Not applicable

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

N/A

Blinding：

N/A

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

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）：

Not stated

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：

Not stated

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

Not stated

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2021-11-28 10:52:27