ChiCTR2600118400 版本V1.0 版本创建时间2026/02/05 08:46:14 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：

 ChiCTR2600118400 

最近更新日期：

Date of Last Refreshed on：

 2026-02-05 08:46:07 

注册时间：

Date of Registration：

 2026-02-05 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

皮肤试验用结核分枝杆菌抗原(EM)用于结核病患者与健康受试者的安全性、耐受性与初步有效性的单中心、开放I期临床研究

Public title：

A Phase I, single-center, open-label clinical study on the safety, tolerability, and preliminary efficacy of Mycobacterium tuberculosis antigen (EM) for skin testing in patients with tuberculosis and healthy participants

注册题目简写：

English Acronym：

研究课题的正式科学名称：

皮肤试验用结核分枝杆菌抗原(EM)用于结核病患者与健康受试者的安全性、耐受性与初步有效性的单中心、开放I期临床研究

Scientific title：

A Phase I, single-center, open-label clinical study on the safety, tolerability, and preliminary efficacy of Mycobacterium tuberculosis antigen (EM) for skin testing in patients with tuberculosis and healthy participants

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：

晏和贵 

研究负责人：

刘冠 

Applicant：

Yan Hegui  

Study leader：

Liu Guan 

申请注册联系人电话：

Applicant telephone：

 +86 27 83602146

研究负责人电话：

Study leader's
telephone：

+86 27 83602146

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：

 18184819378@163.com

研究负责人电子邮件：

Study leader's E-mail：

 176231931@qq.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：

湖北省武汉市硚口区宝丰路28号

研究负责人通讯地址：

湖北省武汉市硚口区宝丰路28号

Applicant address：

No. 28, Baofeng Road, Qiaokou District, Wuhan City, Hubei Province

Study leader's address：

No. 28, Baofeng Road, Qiaokou District, Wuhan City, Hubei Province

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：

武汉市肺科医院

Applicant's institution：

Wuhan Pulmonary Hospital

研究负责人所在单位：

武汉市肺科医院

Affiliation of the Leader：

Wuhan Pulmonary Hospital

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：

 2023-085

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：

武汉市肺科医院医学伦理审查委员会

Name of the ethic committee：

Medical Ethics Committee of Wuhan Pulmonary Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2023-10-26 00:00:00

伦理委员会联系人：

王敏

Contact Name of the ethic committee：

Wang Min

伦理委员会联系地址：

湖北省武汉市硚口区宝丰路28号

Contact Address of the ethic committee：

No. 28, Baofeng Road, Qiaokou District, Wuhan City, Hubei Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 27 83613724

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 whsfkyyllsc@163.com

研究实施负责（组长）单位：

武汉市肺科医院

Primary sponsor：

Wuhan Pulmonary Hospital

研究实施负责（组长）单位地址：

湖北省武汉市硚口区宝丰路28号

Primary sponsor's address：

No. 28, Baofeng Road, Qiaokou District, Wuhan City, Hubei Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

湖北省

市(区县)：

Country：

China

Province：

Hubei

City：

单位(医院)：

武汉市肺科医院

具体地址：

湖北省武汉市硚口区宝丰路28号

Institution
hospital：

Wuhan Pulmonary Hospital

Address：

No. 28, Baofeng Road, Qiaokou District, Wuhan City, Hubei Province

经费或物资来源：

安博智联（苏州）生物科技有限公司

Source(s) of funding：

Ambo Intelligence (Suzhou) Biotechnology Co., Ltd.

研究疾病：

肺结核  

Target disease：

Pulmonary Tuberculosis

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：

非随机对照试验 

Study design：

Non randomized control 

研究目的：

主要目的： 1)结核病患者与健康受试者注射不同剂量EM的安全性与耐受性； 2)结核病患者中不同浓度EM皮试检出阳性率，健康受试者中不同浓度EM皮试阴性符合率。 次要目的： 1)观察EM皮肤迟发性超敏反应发生、发展与消失过程； 2)为II期临床研究选择合适的剂量，将于3个剂量中选择2个剂量； 3)评估EM与同用途IGRA反应一致性； II期和III期临床研究EM与EC反应结果不一致时需以IGRA进行第三种试剂验证，样品采样需在皮试后进行，本研究进行皮试前后取样检测，评估皮试后取样是否对IGRA检测结果产生影响。  

Objectives of Study：

Primary Objectives: 1.To evaluate the safety and tolerability of different doses of EM when administered to tuberculosis patients and healthy participants; 2.To determine the positive detection rate of EM skin tests at different concentrations in tuberculosis patients, and the negative compliance rate of EM skin tests at different concentrations in healthy participants. Secondary Objectives: 1.To observe the occurrence, development, and resolution of delayed-type hypersensitivity reactions to EM; 2.To select appropriate doses for Phase II clinical trials, with 2 doses to be chosen from 3 candidates; 3.To assess the consistency of reactions between EM and IGRA (which serves the same purpose); In cases of inconsistent results between EM and EC in Phase II and III clinical trials, IGRA shall be used as a third reagent for verification. Sample collection should be performed after skin tests. In this study, samples will be collected and tested both before and after skin tests to evaluate whether post-skin-test sampling affects IGRA test results.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1. 结核病患者入选标准： （1)已确诊的结核病患者，或本次已开始抗结核治疗的结核病患者疗程最好为14天内，最长不超过1个月（本次开始治疗与前次治疗停药间隔大于6个月）；年龄16至65周岁男女不限； （2)符合《中华人民共和国卫生行业标准肺结核诊断标准（WS288-2017）》判定诊断为肺结核的受试者（认可临床上经综合分析做出的诊断）； （3)病原学阳性肺结核患者需提供检查阳性的结果，包括但不限于痰涂片阳性、分枝杆菌分离培养阳性、结核分枝杆菌基因检测阳性和肺组织病理学检查阳性。病原学阴性患者比例>=50%； （4)本人承诺能遵守临床试验方案的要求参加随访，同意参加本试验并签署知情同意书； （5)育龄女性受试者（处于女性生殖器官发育成熟（月经初潮）到卵巢功能衰退（绝经）后一年内的女性）入组前妊娠试验检测阴性，并在入选本研究前2周内已采取有效的避孕措施，且在入组后28天内无生育计划，并承诺采取有效的避孕措施（包括：口服避孕药、注射或埋植避孕、缓释局部避孕药、激素贴剂、宫内节育器（IUD）、绝育、避免性生活、安全套（男性）、隔膜、宫颈帽等；不视为有效的避孕措施为安全期避孕法、体外射精法和紧急避孕法等）。 2. 健康受试者入选标准： (1)*年龄16-65岁，男女不限，入组当天腋下体温<=37.3℃； (2)本人承诺能遵守临床试验方案的要求参加随访，同意参加本试验并签署知情同意书； (3)经病史询问无结核病史、结核病家族史、结核病密切接触史（指与登记的肺结核患者在其确诊前3个月至开始抗结核治疗后14天内直接接触），无肺内、外结核病，无可能为结核病的呼吸道症状及全身其它部位症状。胸部影像学检查无异常者； (4)无结核病中毒临床症状（结核中毒症状是指除外咳嗽、胸痛、胸闷等局部症状外，尚有较为明显的全身症状，如乏力、午后低热、食欲不振、夜间盗汗等。女性可能有内分泌系统的紊乱，比如月经不调、闭经等）； (5)经问诊既往无心、肝、肾、消化道、神经系统、精神异常及代谢异常病史； (6)*体格检查、心电图、生命体征以及实验室检查包括血常规、血生化、尿常规各项检查均正常或异常无临床意义； (7)育龄女性受试者（处于女性生殖器官发育成熟（月经初潮）到卵巢功能衰退（绝经）后一年内的女性）入组前妊娠试验检测阴性，并在入选本研究前2周内已采取有效的避孕措施，且在入组后28天内无生育计划，并承诺采取有效的避孕措施（包括：口服避孕药、注射或埋植避孕、缓释局部避孕药、激素贴剂、宫内节育器（IUD）、绝育、避免性生活、安全套（男性）、隔膜、宫颈帽等；不视为有效的避孕措施为安全期避孕法、体外射精法和紧急避孕法等）。 如果受试者不符合带星号（*）规定的标准，可以在符合此标准时重新安排访视。

Inclusion criteria

1. Inclusion criteria for tuberculosis patients: (1) Patients with confirmed tuberculosis or tuberculosis patients who have started anti-tuberculosis therapy should preferably be within 14 days and no more than 1 month (the interval between the start of treatment and the discontinuation of the previous treatment is greater than 6 months); Male or female aged 16 to 65; (2) Subjects who meet the "Diagnostic Criteria for Pulmonary Tuberculosis of the People's Republic of China Health Industry Standard (WS288-2017)" (recognized diagnosis made by comprehensive clinical analysis); (3) Patients with positive etiology-positive pulmonary tuberculosis need to provide positive test results, including but not limited to positive sputum smear, positive mycobacterial isolation culture, positive Mycobacterium tuberculosis genetic test, and positive lung histopathology test. The proportion of patients with negative etiology >=50%; (4) I promise to comply with the requirements of the clinical trial protocol to participate in the follow-up, agree to participate in this trial and sign the informed consent form; (5) Female subjects of childbearing age (women within one year after the development and maturity of female reproductive organs (menarche) to ovarian function decline (menopause)) have a negative pregnancy test test before enrollment, and have taken effective contraceptive measures within 2 weeks before inclusion in this study, and have no birth plan within 28 days after enrollment, and commit to taking effective contraceptive measures (including: oral contraceptives, injectable or implanted contraception, extended-release topical contraceptives, hormone patches, intrauterine devices (IUDs), sterilization, avoidance of sexual activity, Condoms (males), diaphragms, cervical caps, etc.; Contraceptive measures that are not considered effective are safe period contraception, external ejaculation method, emergency contraception, etc.). 2. Healthy Subject Inclusion Criteria: (1) *Age 16-65 years old, male or female, axillary body temperature <=37.3°C on the day of enrollment; (2) I promise to comply with the requirements of the clinical trial protocol to participate in the follow-up, agree to participate in this trial and sign the informed consent form; (3) No history of tuberculosis, family history of tuberculosis, and close contact with tuberculosis (referring to direct contact with registered tuberculosis patients within 3 months before diagnosis to 14 days after starting anti-tuberculosis therapy), no internal or external tuberculosis, and no respiratory symptoms of tuberculosis and other parts of the body. Chest imaging examination without abnormalities; (4) No clinical symptoms of tuberculosis poisoning (tuberculosis poisoning symptoms refer to local symptoms such as cough, chest pain, and chest tightness, as well as obvious systemic symptoms, such as fatigue, low-grade fever in the afternoon, loss of appetite, night sweats, etc.) Women may have endocrine system disorders, such as irregular menstruation, amenorrhea, etc.); (5) No history of heart, liver, kidney, digestive tract, nervous system, mental and metabolic abnormalities after consultation; (6) *Physical examination, electrocardiogram, vital signs and laboratory examinations including blood routine, blood biochemistry, and urine routine are normal or abnormal and have no clinical significance; (7) Female subjects of childbearing age (women who are in the maturity of female reproductive organs (menarche) and within one year after ovarian function decline (menopause)) have a negative pregnancy test test before enrollment, and have taken effective contraceptive measures within 2 weeks before inclusion in this study, and have no birth plan within 28 days after enrollment, and commit to taking effective contraceptive measures (including: oral contraceptives, injectable or implanted contraception, extended-release topical contraceptives, hormone patches, intrauterine devices (IUDs), sterilization, avoidance of sexual activity, Condoms (males), diaphragms, cervical caps, etc.; Contraceptive measures that are not considered effective are safe period contraception, external ejaculation method, emergency contraception, etc.). If the subject does not meet the criteria specified by the asterisk (*), the visit may be rescheduled if this criterion is met.

排除标准：

1.*入组前3个月内进行过结核菌素（PPD）或同类产品皮肤试验； 2.患急性传染病（如麻疹、百日咳、流行性感冒、肺炎等）、急性眼结膜炎、急性中耳炎、广泛性皮肤病及过敏体质（对两种或以上药物或食物有过敏史者，或已知对本药组分有过敏以及疤痕体质）者； 3.患有先天畸形、发育障碍及先天性疾病以及任何严重疾病，如：渐进性粥样硬化症或血糖控制不佳、研究者判断不适宜参加试验的糖尿病、需要吸氧治疗的慢性阻塞性肺病、急性或渐进性肝病或肾病、充血性心力衰竭、有皮疹及脓皮病者等疾病者； 4.有惊厥、癫痫、脑病和神经系统症状或体征病史者； 5.有已知或可疑（或有高危发生可能）的免疫功能损伤或异常者，包括： (1)*3个月内或正在接受免疫抑制剂（包括化疗）或免疫增强剂治疗者，如长期使用全身性糖皮质激素治疗（连续2周及以上使用，剂量2mg/kg/天或20mg/天泼尼松或相当于泼尼松剂量；允许局部用药（如软膏、滴眼液、吸入剂或鼻喷剂））、胸腺肽、白介素、干扰素、香菇多糖，BCG-PSN等； (2)*3个月内接受免疫球蛋白制剂或血液产品或血浆提取治疗者； (3)恶性肿瘤患者； (4)HIV感染者； 6.*急性发热性疾病者（结核病患者除外）； 7.*皮试前7天内接种过非活疫苗，或28天内接种过减毒活疫苗； 8.正在参加或在本次临床研究前3个月内参加过其他任何临床研究者； 9.妊娠期、哺乳期妇女； 10.*有明确高血压史且药物控制后收缩压>=150 mmHg和/或舒张压>=100 mmHg； 11.怀疑或确有药物滥用、酗酒者；精神和躯体残疾影响皮试注射结果观察者； 12.研究者认为存在依从性差等有可能影响试验评估的任何情况。 对于带星号（*）的标准，如果受试者具有该标准规定的情形，可以在不再具有这些情形时重新安排访视。

Exclusion criteria：

1.*Skin test of tuberculin (PPD) or similar products within 3 months prior to enrollment; 2. Suffering from acute infectious diseases (such as measles, whooping cough, influenza, pneumonia, etc.), acute ocular conjunctivitis, acute otitis media, generalized skin diseases and allergies (those who have a history of allergy to two or more drugs or foods, or known allergies and scars to the components of this drug); 3. Suffering from congenital malformations, developmental disorders, congenital diseases, and any serious diseases, such as: progressive atherosclerosis or poor blood sugar control, diabetes mellitus judged by the investigator to be unsuitable for the trial, chronic obstructive pulmonary disease requiring oxygen therapy, acute or progressive liver disease or kidney disease, congestive heart failure, skin rash and pyoderma and other diseases; 4. Those who have a history of convulsions, epilepsy, encephalopathy, and neurological symptoms or signs; 5. Those who have known or suspected (or high-risk) immune damage or abnormalities, including: (1) *Those who are receiving immunosuppressants (including chemotherapy) or immuno-enhancer therapy within 3 months, such as long-term use of systemic glucocorticoids (2 consecutive weeks or more, dose of 2mg/kg/day or 20mg/day prednisone or equivalent); Topical medications (such as ointments, eye drops, inhalants, or nasal sprays)), thymus peptides, interleukins, interferons, shiitake polysaccharides, BCG-PSN, etc. are allowed; (2) *Those who have received immunoglobulin preparations or blood products or plasma extraction treatment within 3 months; (3) Patients with malignant tumors; (4) HIV-infected individuals; 6.*Acute febrile illness (except tuberculosis patients); 7. *Vaccination with non-live vaccines within 7 days or live attenuated vaccines within 28 days before the skin test; 8. Is participating in or has participated in any other clinical investigator within 3 months before this clinical study; 9. Pregnant and lactating women; 10.*Has a clear history of hypertension and systolic blood pressure >=150 mmHg and/or diastolic blood pressure >=100 mmHg after drug control; 11. Suspected or confirmed drug abuse or alcoholism; Observers whose mental and physical disabilities affect the results of skin test injections; 12. Any condition that the investigator believes may affect the evaluation of the trial, such as poor compliance. For criteria marked with an asterisk (*), if the subject has the conditions specified in that criterion, the visit can be rescheduled if they no longer have those conditions.

研究实施时间：

Study execute time：

从 From 2023-11-09 00:00:00至 To 2024-09-14 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-11-30 00:00:00 至 To 2024-01-30 00:00:00

干预措施：

Interventions：

组别：

健康参与者中剂量组（5U/0.1ml）

样本量：

 10

Group：

Medium-Dose Group of Healthy Participants (5U/0.1ml)

Sample size：

干预措施：

在参与者左臂或右臂皮内注射0.1ml结核分枝杆菌抗原(EM)

干预措施代码：

Intervention：

Intradermally inject 0.1ml of Mycobacterium tuberculosis antigen (EM) into either the left or right arm of the participants

Intervention code：

组别：

健康参与者高剂量组（10U/0.1ml）

样本量：

 10

Group：

High-Dose Group of Healthy Participants(10U/0.1ml)

Sample size：

干预措施：

在参与者左臂或右臂皮内注射0.1ml结核分枝杆菌抗原(EM)

干预措施代码：

Intervention：

Intradermally inject 0.1ml of Mycobacterium tuberculosis antigen (EM) into either the left or right arm of the participants

Intervention code：

组别：

结核患者中剂量组（5U/0.1ml）

样本量：

 10

Group：

Medium-Dose Group of Tuberculosis Patients (5U/0.1ml)

Sample size：

干预措施：

在患者左臂或右臂皮内注射0.1ml结核分枝杆菌抗原(EM)

干预措施代码：

Intervention：

Intradermally inject 0.1ml of Mycobacterium tuberculosis antigen (EM) into either the left or right arm of the patients

Intervention code：

组别：

结核患者低剂量组（2.5U/0.1ml）

样本量：

 10

Group：

Low-Dose Group of Tuberculosis Patients (2.5U/0.1ml)

Sample size：

干预措施：

在患者左臂或右臂皮内注射0.1ml结核分枝杆菌抗原(EM)

干预措施代码：

Intervention：

Intradermally inject 0.1ml of Mycobacterium tuberculosis antigen (EM) into either the left or right arm of the patients

Intervention code：

组别：

结核患者高剂量组（10U/0.1ml）

样本量：

 10

Group：

High-Dose Group of Tuberculosis Patients (10U/0.1ml)

Sample size：

干预措施：

在患者左臂或右臂皮内注射0.1ml结核分枝杆菌抗原(EM)

干预措施代码：

Intervention：

Intradermally inject 0.1ml of Mycobacterium tuberculosis antigen (EM) into either the left or right arm of the patients

Intervention code：

组别：

健康参与者低剂量组（2.5U/0.1ml）

样本量：

 10

Group：

Low-Dose Group of Healthy Participants

Sample size：

干预措施：

在参与者左臂或右臂皮内注射0.1ml结核分枝杆菌抗原(EM)

干预措施代码：

Intervention：

Intradermally inject 0.1ml of Mycobacterium tuberculosis antigen (EM) into either the left or right arm of the participants

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 湖北省 

市(区县)：

  

Country：

China

Province：

Hubei

City：

单位(医院)：

 武汉市肺科医院 

单位级别：

 三级甲等 

Institution
hospital：

Wuhan Pulmonary Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

各观察时间点EM在结核病患者中的阳性检出率与硬结、红晕平均直径

指标类型：

主要指标

Outcome：

The positive detection rate of EM and the average diameters of induration and erythema in tuberculosis patients at each observation time point

Type：

Primary indicator

测量时间点：

皮试后至14天

测量方法：

Measure time point of outcome：

From the skin test to 14 days

Measure method：

指标中文名：

结核病患者和健康受试者的中剂量和高剂量组受试者皮试前与皮试后24h、72h和7天的IGRA结果一致性

指标类型：

次要指标

Outcome：

The consistency of IGRA results before and 24 hours, 72 hours, and 7 days after the skin test in the medium-dose and high-dose groups of tuberculosis patients and healthy participants.

Type：

Secondary indicator

测量时间点：

皮试后24h、72h和7天

测量方法：

Measure time point of outcome：

24 hours, 72 hours, and 7 days after the skin test

Measure method：

指标中文名：

各观察时间点结核病患者阳性检出率、健康受试者阴性符合率与IGRA反应一致性

指标类型：

次要指标

Outcome：

The positive detection rate in tuberculosis patients, negative compliance rate in healthy participants, and consistency of IGRA responses at each observation time point

Type：

Secondary indicator

测量时间点：

皮试后至14天

测量方法：

Measure time point of outcome：

From the skin test to 14 days

Measure method：

指标中文名：

各观察时间点EM在健康受试者中的阴性符合率与硬结、红晕平均直径

指标类型：

主要指标

Outcome：

The positive detection rate of EM and the average diameters of induration and erythema in healthy participants at each observation time point

Type：

Primary indicator

测量时间点：

皮试后至14天

测量方法：

Measure time point of outcome：

From the skin test to 14 days

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

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

结束

/Completed

年龄范围：

Participant age：
最小 Min age 16 岁 years
最大 Max age 65 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）：

无

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

None

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：

无

Blinding：

None

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）：

邮件联系研究者

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

Contact the researcher by email

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：

本研究数据直接录入电子数据采集系统（EDC)

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

The data of this study were directly entered into the Electronic Data Capture (EDC) system.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2026-02-05 08:46:07