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：	ChiCTR2500105903
最近更新日期： Date of Last Refreshed on：	2025-07-14 16:12:13
注册时间： Date of Registration：	2025-07-14 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	一项评价雾化吸入脐带间充质干细胞外泌体（MSC-Exo）治疗中至重度哮喘的安全性和耐受性的单中心、随机、单臂Ⅰ期临床研究
Public title：	A single center, randomized, single arm phase I clinical study evaluating the safety and tolerability of nebulized inhalation of umbilical cord mesenchymal stem cell exosomes (MSC Exo) in the treatment of moderate to severe asthma
注册题目简写：
English Acronym：
研究课题的正式科学名称：	一项评价雾化吸入脐带间充质干细胞外泌体（MSC-Exo）治疗中至重度哮喘的安全性和耐受性的单中心、随机、单臂Ⅰ期临床研究
Scientific title：	A single center, randomized, single arm phase I clinical study evaluating the safety and tolerability of nebulized inhalation of umbilical cord mesenchymal stem cell exosomes (MSC Exo) in the treatment of moderate to severe asthma
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：	宋西成	研究负责人：	宋西成; 张宇
Applicant：	Song Xicheng	Study leader：	Song Xicheng; Zhang Yu
申请注册联系人电话： Applicant telephone：	+86 180 0535 0077	研究负责人电话： Study leader's telephone：	+86 180 0535 0077
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：	drxchsong@163.com	研究负责人电子邮件： Study leader's E-mail：	drxchsong@163.com
申请单位网址(自愿提供)： Applicant website(voluntary supply)：	烟台毓璜顶医院	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：	山东省烟台市芝罘区毓璜顶东路20号	研究负责人通讯地址：	山东省烟台市芝罘区毓璜顶东路20号
Applicant address：	No. 20, Yuhuangding East Road, Zhifu District, Yantai, Shandong	Study leader's address：	No. 20, Yuhuangding East Road, Zhifu District, Yantai, 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：	烟台毓璜顶医院
Applicant's institution：	Yantai Yuhuangding Hospital
研究负责人所在单位：	烟台毓璜顶医院
Affiliation of the Leader：	Yantai Yuhuangding 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：	YYYIRB-IIT[2025]007	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：	烟台毓璜顶医院临床研究伦理委员会
Name of the ethic committee：	Clinical Research Ethics Committee of Yantai Yuhuangding Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2025-04-14 00:00:00
伦理委员会联系人：	李康琪
Contact Name of the ethic committee：	Li Kangqi
伦理委员会联系地址：	山东省烟台市芝罘区毓璜顶东路20号
Contact Address of the ethic committee：	No. 20, Yuhuangding East Road, Zhifu District, Yantai, Shandong
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 535 622 9756	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：

烟台毓璜顶医院

Primary sponsor：

Yantai Yuhuangding Hospital

研究实施负责（组长）单位地址：

山东省烟台市芝罘区毓璜顶东路20号

Primary sponsor's address：

No. 20, Yuhuangding East Road, Zhifu District, Yantai, 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)：	山东	市(区县)：
Country：	China	Province：	Shandong	City：
单位(医院)：	烟台毓璜顶医院	具体地址：	山东省烟台市芝罘区毓璜顶东路20号
Institution hospital：	Yantai Yuhuangding Hospital	Address：	No. 20, Yuhuangding East Road, Zhifu District, Yantai, Shandong

经费或物资来源：

山东省齐鲁细胞治疗工程技术有限公司

Source(s) of funding：

Shandong Qilu Cell Therapy Engineering Technology Co., Ltd

研究疾病：

哮喘

Target disease：

Asthma

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：

单臂

Study design：

Single arm

研究目的：

评价MSC-Exo雾化给药在中至重度哮喘患者治疗中的安全性和耐受性，并为随后有效性临床研究提供临床剂量参考

Objectives of Study：

Evaluate the safety and tolerability of MSC Exo nebulization in the treatment of moderate to severe asthma patients, and provide clinical dose references for subsequent efficacy clinical studies

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) When signing the informed consent form, the age range is between 18 and 65 (including both ends), male or female, and diagnosed with asthma for at least 12 months.
2) Smoking history with a total of less than 10 packs per year and no smoking in at least the past 12 months;
3) Voluntarily participate in this clinical study and sign the informed consent form, and be able to comply with the clinical visit plan and research related procedures.
4) According to the 2023 GINA guidelines and the 2020 version of the Asthma Prevention and Treatment Guidelines, individuals who have been receiving medium to high doses of ICS combined with one or two control drugs for at least 28 days prior to randomization and have achieved basic control (≥ 20 points) in ACT score within the first 2 months of randomization. Note: Medium to high dose ICS: equivalent to ≥ 500 μ g of fluticasone propionate or equivalent per day. ICS can be included in compound preparations. Control drugs: including LABA, LTRA, LAMA, theophylline.
5) At screening and baseline visits, FEV1 ≥ 60% before using bronchodilators (trough value).
6) Previous positive results in bronchial dilation test or provocation test (FEV1 improvement rate>12% and absolute value increase>200 mL).
7) ACT score >= 20.
8) During the screening period, based on the researcher's judgment, the subjects demonstrated acceptable inhalers, peak flow meters, and pulmonary function testing techniques.
9) Comply with contraception requirements.
10) There is no allergic reaction to the components of the test reagent.

排除标准：

1. 经研究者判断，目前患有其他可能损伤肺功能（与后期评估效果相关）的呼吸系统疾病（例如，活动性肺部感染、慢性阻塞性肺疾病、支气管扩张、肺纤维化、囊性纤维化等） 2. 筛查前既往或当前有异常生命体征史、异常实验室检查结果、临床相关心电图异常或心血管疾病的受试者被排除在研究之外（COPD研究的排除标准描述） 3. 有已知或疑似免疫抑制病史（即使感染已消退），包括侵袭性机会性感染病史（例如曲霉病、球孢子菌病、组织胞浆菌病、李斯特菌病和肺孢子虫病等）；或不寻常的频发性、复发性或长期感染。 4. （疑似）活动性结核病史；或未经治疗的潜伏性结核病或未得到标准治疗的结核病，除非研究者判断患者已得到充分治疗。 5. 乙型肝炎、丙肝或 HIV 感染者，或筛选时存在以下病毒学检查异常（满足以下任一者）：（1）乙型肝炎表面抗原（HbsAg）阳性；（2）乙型肝炎核心抗体（HbcAb）阳性，且HBV-DNA 定量检测结果高于检测下限；（3）丙型肝炎病毒抗体（HCV Ab）阳性，且HCV-RNA定量检测结果高于检测下限；（4）人类免疫缺陷病毒抗体（HIV Ab）阳性。 6. 恶性肿瘤病史：患有宫颈原位癌、非转移性皮肤鳞癌或基底细胞癌者，在签署知情前已完成治愈性治疗至少12个月，可进入本研究；患有其他恶性肿瘤的受试者，在签署知情前已完成治愈性治疗至少5年，可以进入本研究 7. 随机前12个月内接受过支气管热成形术。 8. 签署知情前4周至随机化前，全身性糖皮质激素治疗者（用于哮喘急性发作使用的SCS除外；外用、眼科、鼻内使用糖皮质激素者除外）。 9. 随机前3个月内或5个半衰期内（以较长者为准），参加过任何药物或医疗器械的干预性临床试验。 10.随机前3个月内，接受过特异性免疫治疗。 11.随机前30天内接受过静脉注射人免疫球蛋白（IVIG）或血液制品。 12.随机前30天内接种过（减毒）活疫苗或计划在研究期间接种（减毒）活疫苗。 13. 筛选期出现下列实验室检查异常：（1）嗜酸粒细胞>1500个细胞/mm3 或1.5×109/L （2）血小板<80,000个细胞/mm3 或80×109/L （3）磷酸肌酸激酶（CPK）>5倍ULN （4）ALT>3倍ULN （5）AST>3倍ULN （6）胆红素≥2倍ULN 14.怀孕或哺乳期的妇女； 15. 疑似或明确的吸毒史； 16.心脏疾病，包括以下情况之一：急性冠状动脉综合征、急性心力衰竭[纽约心脏协会（NYHA）分类为III或IV级]、室性心律失常（持续性室性心动过速、心室颤动、复苏性猝死）、NYHA分类为III级或IV级心力衰竭、永久性起搏无法预防的严重传导障碍（房室传导阻滞2和3、窦房传导阻滞）、3个月内病因不明的晕厥或高血压失控及筛查12导联心电图时出现临床显著异常者； 17. 入组前4周内哮喘加重（包括急诊室、紧急护理或因哮喘导致的医院就诊，导致哮喘相关药物增加）； 18. 既往雾化吸入治疗后出现不耐受或有哮喘症状加重的； 19. 研究者认为可能影响受试者安全性、或影响疗效评估、或妨碍受试者完成整个研究的任何具有临床意义的检查异常或严重和/或未能控制的疾病（史）（包括但不限于：严重的神经系统疾病、严重的精神障碍史、重大心血管疾病、严重心律失常等）或其他因素；有严重的合并症，研究者认为这可能会损害患者的安全性或依从性，或妨碍研究的成功完成。

Exclusion criteria：

1.According to the researchers' assessment, there are currently other respiratory system diseases that may damage lung function (related to later evaluation effects), such as active lung infections, chronic obstructive pulmonary disease, bronchiectasis, pulmonary fibrosis, cystic fibrosis, etc 2. Subjects with a history or current history of abnormal vital signs, abnormal laboratory test results, clinically relevant electrocardiogram abnormalities, or cardiovascular disease prior to screening were excluded from the study (description of exclusion criteria for COPD studies) 3. Have a known or suspected history of immunosuppression (even if the infection has subsided), including a history of invasive opportunistic infections (such as aspergillosis, coccidiomycosis, histiocytosis, listeriosis, and Pneumocystis disease); Or unusual frequent, recurrent, or long-term infections. 4. (Suspected) history of active tuberculosis; Or untreated latent tuberculosis or tuberculosis without standard treatment, unless the researcher judges that the patient has been adequately treated. 5. Individuals infected with hepatitis B, hepatitis C, or HIV, or those with abnormal virological tests during screening (meeting any of the following criteria): (1)Positive for hepatitis B surface antigen (HbsAg); (2)Hepatitis B core antibody (HbcAb) is positive, and the HBV-DNA quantitative test result is higher than the detection limit; (3)Hepatitis C virus antibody (HCV Ab) is positive, and the HCV-RNA quantitative detection result is higher than the detection limit; (4)Positive for Human Immunodeficiency Virus Antibody (HIV Ab). 6. History of malignant tumors: Patients with cervical carcinoma in situ, non metastatic squamous cell carcinoma of the skin, or basal cell carcinoma who have completed curative treatment for at least 12 months before signing the informed consent form are eligible to enter this study; Subjects with other malignant tumors who have completed curative treatment for at least 5 years before signing the informed consent form are eligible to enter this study 7. Received bronchial thermoplasty within the first 12 months of randomization. From 4 weeks prior to signing the informed consent agreement to randomization, systemic corticosteroid treatment (excluding SCS used for acute asthma attacks) is required; Except for topical, ophthalmic, and intranasal use of glucocorticoids. 9. Have participated in any interventional clinical trials of drugs or medical devices within the first 3 months or 5 half lives (whichever is longer) prior to randomization. 10. Received specific immunotherapy within the first 3 months of randomization. 11. Received intravenous injection of human immunoglobulin (IVIG) or blood products within the first 30 days of randomization. 12. Have received (attenuated) live vaccine within the first 30 days of randomization or plan to receive (attenuated) live vaccine during the study period. 13.During the screening period, the following laboratory test abnormalities occurred: (1)Eosinophils>1500 cells/mm3 or 1.5 × 10^9/L (2)Platelets<80000 cells/mm3 or 80 × 10^9/L (3)Phosphocreatine kinase (CPK)>5-fold ULN (4)ALT>3 times ULN (5)AST>3 times ULN (6)Bilirubin >= 2 times ULN 14. Pregnant or lactating women; 15. Suspected or clear history of drug use; 16. Heart disease, including one of the following conditions: acute coronary syndrome, acute heart failure [classified as grade III or IV by the New York Heart Association (NYHA)], ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, sudden resuscitation death), NYHA classified as grade III or IV heart failure, severe conduction disorders that cannot be prevented by permanent pacing (atrioventricular block 2 and 3, sinoatrial block), syncope or uncontrolled hypertension of unknown cause within 3 months, and clinically significant abnormalities during screening of 12 lead electrocardiograms; Within the first 4 weeks of enrollment, asthma worsened (including visits to the emergency room, emergency care, or hospitals due to asthma, resulting in an increase in asthma related medications); 18. Those who have developed intolerance or worsened asthma symptoms after previous nebulization therapy; 19. Any clinically significant examination abnormalities or serious and/or uncontrolled diseases (history) (including but not limited to: severe neurological disorders, severe mental disorders, major cardiovascular diseases, severe arrhythmias, etc.) or other factors that the researchers believe may affect the safety of the subjects, or affect efficacy evaluation, or hinder the completion of the entire study; There are serious complications that researchers believe may compromise patient safety or compliance, or hinder the successful completion of the study.

研究实施时间：

Study execute time：

从 From 2025-02-28 00:00:00至 To 2026-03-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-07-15 00:00:00 至 To 2026-03-31 00:00:00

干预措施：

Interventions：

组别：	队列 1	样本量：	6
Group：	Queue 1	Sample size：	6
干预措施：	0.5×10^9particles /3mL / 次，共 2.5×10^9 particles / 人	干预措施代码：
Intervention：	0.5 × 10^9 particles/3mL/time, a total of 2.5 × 10^9 particles/person	Intervention code：

组别：	队列 2	样本量：	6
Group：	Queue 2	Sample size：	6
干预措施：	2×10^9 particles / 3mL / 次，共 8.0×10^9particles /人	干预措施代码：
Intervention：	2 × 10^9 particles/3mL/time, a total of 8.0 × 10^9 particles/person	Intervention code：

组别：	队列 3	样本量：	6
Group：	Queue 3	Sample size：	6
干预措施：	8×10^9 particles / 3mL / 次，共 4.0×10^10 particles / 人	干预措施代码：
Intervention：	8 × 10 ^ 9 particles/3mL/time, a total of 4.0 × 10 ^ 10 particles/person	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)：
Country：	China	Province：	Shandong	City：
单位(医院)：	烟台毓璜顶医院	单位级别：	三甲
Institution hospital：	Yantai Yuhuangding Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	最大耐受剂量（MTD）	指标类型：	主要指标
Outcome：	Maximum Tolerant Dose (MTD)	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	生命体征	指标类型：	次要指标
Outcome：	Vital signs	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	血常规、尿常规、肝功能、肾功能	指标类型：	次要指标
Outcome：	Blood routine, urine routine, liver function, kidney function	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	12导联心电图	指标类型：	次要指标
Outcome：	12-lead ecg	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	ACT评分	指标类型：	次要指标
Outcome：	ACT rating	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：	无	组织：
Sample Name：	None	Tissue：
人体标本去向	其它	说明
Fate of sample：	0thers	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	18	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:

公开/Public

盲法：
Blinding：
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	无
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	None
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：	病例记录表
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Case Record Form
数据与安全监察委员会： Data and Safety Monitoring Committee：	暂未确定/Not yet
注册人： Name of Registration：	2025-07-14 16:12:08