ChiCTR2500110119 版本V1.0 版本创建时间2025/09/30 15:51:06 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：

 ChiCTR2500110119 

最近更新日期：

Date of Last Refreshed on：

 2025-09-30 15:51:00 

注册时间：

Date of Registration：

 2025-09-30 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

一项考察经颅骨骨髓注射RK-4注射液治疗急性大脑半球大面积梗死的单臂、开放标签、盲终点的Ib/IIa研究

Public title：

A single-arm, open-label, blind-endpoint Ib/IIa study investigating the treatment of acute large cerebral hemisphere infarction with RK-4 injection through cranial bone marrow

注册题目简写：

English Acronym：

研究课题的正式科学名称：

一项考察经颅骨骨髓注射RK-4注射液治疗急性大脑半球大面积梗死的单臂、开放标签、盲终点的Ib/IIa研究

Scientific title：

A single-arm, open-label, blind-endpoint Ib/IIa study investigating the treatment of acute large cerebral hemisphere infarction with RK-4 injection through cranial bone marrow

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：

华垚 

研究负责人：

王伊龙 

Applicant：

Hua Yao 

Study leader：

Wang Yilong  

申请注册联系人电话：

Applicant telephone：

 +86 138 1400 0160

研究负责人电话：

Study leader's
telephone：

+86 139 1166 6571

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：

 huayao@neurodawn.cn

研究负责人电子邮件：

Study leader's E-mail：

 yilong528@aliyun.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：

中国江苏省南京市江宁区福英路天印健康创新园 A3栋

研究负责人通讯地址：

北京市丰台区南四环西路119号

Applicant address：

Building A3, Tianyin Health Innovation Park, Fuying Road, Jiangning District, Nanjing, Jiangsu, China

Study leader's address：

No. 119, South Fourth Ring West Road, Fengtai District, Beijing

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：

福州宁丹榕康生物医药科技有限公司

Applicant's institution：

Fuzhou Neurodawn Rongkang Pharmaceutical Co., LTD

研究负责人所在单位：

首都医科大学附属北京天坛医院

Affiliation of the Leader：

Beijing Tiantan Hospital, Capital Medical University

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：

 YW2025-037-02

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：

首都医科大学附属北京天坛医院伦理委员会

Name of the ethic committee：

Ethics Committee of Beijing Tiantan Hospital, Capital Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

 2025-09-01 00:00:00

伦理委员会联系人：

徐灵灵

Contact Name of the ethic committee：

Xu Lingling

伦理委员会联系地址：

北京市丰台区南四环西路119号北京天坛医院B区行政楼6层606室

Contact Address of the ethic committee：

Room 606, 6th Floor, Administration Building, Area B, Beijing Tiantan Hospital, No. 119, South Fourth Ring West Road, Fengtai District, Beijing

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 10 5997 8555

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：

首都医科大学附属北京天坛医院

Primary sponsor：

Beijing Tiantan Hospital, Capital Medical University

研究实施负责（组长）单位地址：

北京市丰台区南四环西路119号

Primary sponsor's address：

No. 119, South Fourth Ring West Road, Fengtai District, Beijing

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

江苏

市(区县)：

Country：

China

Province：

Jiangsu

City：

单位(医院)：

福州宁丹榕康生物医药科技有限公司

具体地址：

中国江苏省南京市江宁区福英路天印健康创新园 A3栋

Institution
hospital：

Fuzhou Neurodawn Rongkang Biomedical Technology Co., LTD

Address：

Building A3, Tianyin Health Innovation Park, Fuying Road, Jiangning District, Nanjing, Jiangsu, China

经费或物资来源：

企业自筹

Source(s) of funding：

Self-raised funds by enterprises

研究疾病：

急性大脑半球大面积梗死  

Target disease：

Acute large hemispheric infarction

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+II期 

Study phase：

1-2

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

针对存在血管再通治疗禁忌或血管再通治疗效果不佳的急性大脑半球大面积梗死受试者，初步评价经颅骨骨髓注射脑细胞保护剂RK-4注射液的安全性、耐受性以及血浆中的PK特征，并对有效性进行初步探索。  

Objectives of Study：

For subjects with acute large hemispheric infarction who are contraindicated to vascular recanalization or have poor response to vascular recanalization therapy, the safety, tolerability, and PK characteristics of RK-4 injection injected into the brain cell marrow through the cranial bone marrow will be preliminarily evaluated, and the efficacy will be preliminarily explored.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1.18<=年龄＜81周岁，性别不限； 2.本次发病前改良Rankin评分(mRS)评分<=1分； 3.可以在出现神经系统缺损的症状体征后24h内完成给药（醒后卒中或者无目击者卒中受试者，以最后表现正常时间为症状开始时间）； 4.临床症状、体征与影像学诊断为大脑中动脉供血区脑梗死，同时符合以下特征： a)16<=NIHSS评分<=32分，第五项上肢和第六项下肢分数之和>=6； b)影像学提示梗死核心区域：电子计算机扫描灌注成像（CTP）中脑血流量（CBF）＜30%体积或磁共振成像（MRI）弥散加权成像（DWI）序列中表观弥散系数（ADC）值＜620×10-6mm^2/s的病灶体积70-300ml或ASPECTS评分0-6分。优先考虑CTP检查结果，如果CTP和DWI均在筛选期完成，且检查结果不一致时，研究者需综合考虑所有信息（扫描时间、最佳反应梗死尺寸的影像学方法等）作出合理判断并记录；ASPECTS评分基于CTP或MRI均可，但优先基于CTP。 5.如果进行血管再灌注治疗，则治疗效果不佳，同时符合以下条件： a)扩展脑梗死溶栓分级（eTICI）=2a； b)血管再灌注治疗后NIHSS评分未改善或进展且总分仍<=32分。 注：减少1分及以上为改善，增加1分及以上为进展。 6.受试者或其法定代理人自愿签署知情同意书。

Inclusion criteria

1.18 Age <= 81 years old, gender not limited; 2. The modified Rankin Scale (mRS) score was less than or equal to 1 point before the onset of this disease. 3. Administration can be completed within 24 hours after the appearance of symptoms and signs of neurological defects (for those with wake-up stroke or stroke without witnesses, the time when the last normal manifestation occurs is regarded as the onset time of symptoms). 4. The clinical symptoms, signs and imaging diagnosis indicate cerebral infarction in the middle cerebral artery blood supply area, and simultaneously meet the following characteristics: a)16<=NIHSS score <=32 points, the sum of the scores of the fifth upper limb and the sixth lower limb >=6; b) Imaging suggests the core area of infarction: Lesions with cerebral blood flow (CBF) less than 30% in computed tomography perfusion imaging (CTP) or with apparent diffusion coefficient (ADC) value less than 620×10-6mm^2/s in diffusion-weighted imaging (DWI) sequences of magnetic resonance imaging (MRI) ranging from 70 to 300ml or with ASPECTS score ranging from 0 to 6 points. Give priority to the results of CTP examination. If both CTP and DWI are completed during the screening period and the examination results are inconsistent, the researcher needs to make a reasonable judgment by comprehensively considering all information (scanning time, the imaging method that best reflects the size of infarction, etc.) and record it. The ASPECTS score can be based on either CTP or MRI, but CTP is preferred. 5. If vascular reperfusion therapy is performed, the therapeutic effect will be poor, and the following conditions must be met simultaneously: a) Extended thrombolysis grade for Cerebral infarction (eTICI) =2a; b) After vascular reperfusion treatment, the NIHSS score did not improve or progress, and the total score was still <=32 points. Note: A reduction of 1 point or more indicates improvement, while an increase of 1 point or more indicates progress. 6. The subject or his/her legal representative voluntarily signs the informed consent form.

排除标准：

1.并发其他脑血管病满足下列情况之一： a)合并急性期脑出血、蛛网膜下腔出血； b)合并急性期后循环脑梗死，或后循环血管重度狭窄（＞70%）； c)影像学提示脑梗死区域累及双侧； d)筛选前已通过TOAST分型诊断病因明确为颅内动脉夹层、血管炎、烟雾病等其他病因型。 2.梗死区域出血转化，血肿面积>=30% 梗死区域，且具有明显的占位效应； 3.存在脑疝形成的临床体征，例如，单侧或双侧瞳孔扩大、固定；脑水肿相关的意识丧失（NIHSS 1a＞2分），或研究者判断由脑水肿或脑疝形成引起的其他脑干反射丧失；或其他难以控制的生命体征不稳定征象； 4.筛选时计划行颅骨去骨瓣减压术； 5.药物难以控制的顽固性高血压（收缩压＞200mmHg或舒张压＞110mmHg）或低血压（收缩压＜70mmHg或舒张压＜50mmHg）； 6.血糖异常（随机静脉血血糖＜2.8mmol/L或＞23mmol/L）； 7.存在明显的肝功能指标异常或存在明显的肾功能指标异常； 注：明显的肝功能指标异常是指血清丙氨酸氨基转移酶（ALT）或天门冬氨酸氨基转移酶（AST）＞3倍正常值上限（ULN）; 明显的肾功能指标异常是指eGFR 小于60 mL/min/1.73 m^2（eGFR应用CKD-EPI公式进行计算）。 8.过去3个月内，发生了急性ST段抬高型心肌梗塞(MI)，和/或急性失代偿性心力衰竭[符合美国纽约心脏病学会（NYHA）心脏功能分级 III、IV 级）]； 9.存在经颅骨骨髓给药禁忌证，如近3月颅骨骨折、颅骨感染、硬膜下/外血肿、头皮下血肿、头皮皮肤或皮下感染、颅骨板障显示不清等； 10.研究者认为不利于操作的出血倾向,包括但不限于:血小板计数＜100×10^9/L、存在血友病等凝血功能障碍疾病等； 11.存在重度或极重度贫血（血红蛋白＜60g/L）； 12.合并严重呼吸系统疾病（重度慢性阻塞性肺疾病、呼吸衰竭等）需进行气管插管、气管切开或呼吸机进行纠正； 13.筛选前3天内受试者存在严重的局部或全身性感染，包括但不限于因感染出现严重的局部症状，如化脓、剧烈疼痛、组织坏死，或出现明确的全身性感染相关症状，如感染引起的快速出现高热（＞38.5℃）、心率加快、寒战、意识障碍、呼吸困难、休克等； 14.已确诊的严重的CNS退行性疾病，如阿尔茨海默病（AD）、帕金森病（PD）及各种原因所致重度痴呆或者患有精神系统疾病（如精神分裂症、抑郁症等）； 15.既往诊断患有严重的全身性疾病，预计生存期<90天； 16.已知对研究过程治疗药物任意成分以及造影剂过敏； 17.处于妊娠期、哺乳期或存在妊娠可能以及计划妊娠的受试者； 18.受试者无法遵从试验方案或随访要求； 19.筛选前3个月内参加过其他任何干预性临床试验者，或目前正在参加其他任何临床试验者； 20.研究者认为不适合参加本临床研究。

Exclusion criteria：

Concurrent other cerebrovascular diseases meet one of the following conditions: a) Combined with acute cerebral hemorrhage and subarachnoid hemorrhage; b) Combined with acute posterior circulation cerebral infarction, or severe stenosis of posterior circulation vessels (> 70%); c) Imaging suggests that the cerebral infarction area involves both sides; d) Before screening, the etiology was clearly diagnosed as intracranial arterial dissection, vasculitis, Moyamoya disease or other etiological types through TOAST classification. 2. Hemorrhage transformation in the infarcted area, with hematoma area >=30% of the infarcted area, and a significant space-occupying effect; 3. There are clinical signs of brain herniation, for example, unilateral or bilateral pupil dilation and fixation; Loss of consciousness related to brain edema (NIHSS 1a > 2 points), or other brainstem reflex losses determined by researchers to be caused by brain edema or brain herniation formation; Or other uncontrollable signs of unstable vital signs; 4. When screening, it is planned to perform craniectomy and decompressive craniectomy. 5. Intractable hypertension (systolic blood pressure > 200mmHg or diastolic blood pressure > 110mmHg) or hypotension (systolic blood pressure < 70mmHg or diastolic blood pressure < 50 MMHG) that is difficult to control with medication; 6. Abnormal blood glucose (random venous blood glucose < 2.8mmol/L or > 23mmol/L); 7. There are obvious abnormalities in liver function indicators or obvious abnormalities in renal function indicators; Note: Obvious abnormal liver function indicators refer to serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) being greater than three times the upper limit of the normal value (ULN). Obvious abnormal renal function indicators refer to eGFR less than 60 mL/min/1.73 m^2 (eGFR is calculated using the CKD-EPI formula). 8. Within the past three months, acute ST-segment elevation myocardial infarction (MI) and/or acute decompensated heart failure occurred [conforming to the New York Heart Association (NYHA) cardiac function classification of grade III or IV)]; 9. There are contraindications for administration through the skull and bone marrow, such as skull fractures within the last 3 months, skull infections, subdural/epidural hematoma, subcutaneous hematoma of the scalp, scalp skin or subcutaneous infections, and unclear display of the skull board, etc. 10. Bleeding tendencies that researchers consider unfavorable for the operation include but are not limited to: platelet count < 100×10^9/L, presence of coagulation dysfunction diseases such as hemophilia, etc. 11. There is severe or extremely severe anemia (hemoglobin < 60g/L); 12. In cases of severe respiratory diseases (such as severe chronic obstructive pulmonary disease, respiratory failure, etc.), tracheal intubation, tracheotomy or ventilator correction is required. 13. Within 3 days before screening, the subjects had severe local or systemic infections, including but not limited to severe local symptoms due to infection, such as suppuration, severe pain, tissue necrosis, or clear systemic infecation-related symptoms, such as rapid onset of high fever (> 38.5℃), increased heart rate, chills, consciousness disorders, breathing difficulties, shock, etc. caused by infection; 14. Confirmed severe CNS degenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and severe dementia caused by various reasons, or suffering from mental system disorders (such as schizophrenia, depression, etc.); 15. Previously diagnosed with severe systemic diseases, with an expected survival period of less than 90 days; 16. Known to be allergic to any component of the therapeutic drugs used in the research process and contrast agents; 17. Subjects who are pregnant, breastfeeding, have the potential to become pregnant, or are planning to become pregnant; 18. The subjects were unable to comply with the trial protocol or follow-up requirements; 19. Those who have participated in any other interventional clinical trials within the three months prior to screening, or are currently participating in any other clinical trials; 20. The researcher believes that it is not suitable to participate in this clinical study.

研究实施时间：

Study execute time：

从 From 2025-09-30 00:00:00至 To 2026-03-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-09-30 00:00:00 至 To 2026-03-19 00:00:00

干预措施：

Interventions：

组别：

低剂量组

样本量：

 2

Group：

low-dose group

Sample size：

干预措施：

每日1次经颅骨骨髓注射药物RK-4 (1 mg)，连续3天

干预措施代码：

Intervention：

Take drug RK-4 (1 mg ) by transcranial bone marrow injection once daily for consecutive 3 days

Intervention code：

组别：

中剂量组

样本量：

 8

Group：

Medium-dose group

Sample size：

干预措施：

每日1次经颅骨骨髓注射药物RK-4 (2 mg)，连续3天

干预措施代码：

Intervention：

Take drug RK-4 (2 mg ) by transcranial bone marrow injection once daily for consecutive 3 days

Intervention code：

组别：

高剂量组

样本量：

 8

Group：

High-dose group

Sample size：

干预措施：

每日1次经颅骨骨髓注射药物RK-4 (4 mg)，连续3天

干预措施代码：

Intervention：

Take drug RK-4 (4 mg ) by transcranial bone marrow injection once daily for consecutive 3 days

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 北京 

市(区县)：

  

Country：

China

Province：

Beijing

City：

单位(医院)：

 首都医科大学附属北京天坛医院 

单位级别：

 三甲 

Institution
hospital：

Beijing Tiantan Hospital, Capital Medical University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 河北 

市(区县)：

  

Country：

China

Province：

Hebei Province

City：

单位(医院)：

 沧州市中心医院 

单位级别：

 三甲 

Institution
hospital：

Cangzhou Central Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

评价治疗第14+/-1天内经颅骨骨髓注射RK-4注射液治疗急性大脑半球大面积梗死受试者的安全性（不良事件及实验室检查数据在治疗前后的变化）

指标类型：

主要指标

Outcome：

To evaluate the safety of transcranial bone marrow injection of RK-4 injection in the treatment of patients with acute large cerebral hemisphere infarction on the 14th +/- 1st day of treatment (adverse events and changes in laboratory test data before and after treatment)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

评价治疗第14+/-1天内经颅骨骨髓注射RK-4注射液治疗急性大脑半球大面积梗死受试者的耐受性（不良事件及实验室检查数据在治疗前后的变化）

指标类型：

主要指标

Outcome：

To evaluate the tolerance of RK-4 injection through cranial bone marrow on the 14th +/- 1st day of treatment in subjects with acute large cerebral hemisphere infarction (changes in adverse events and laboratory test data before and after treatment)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

评价RK-4经颅骨骨髓注射后在血浆中的药代动力学特征

指标类型：

次要指标

Outcome：

Evaluate the pharmacokinetic characteristics of single ascending doses of RK-4 in patients with LHI by venous blood

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

治疗第14+/-1天NIHSS评分较基线改善>=8分的比例

指标类型：

次要指标

Outcome：

Evaluate the efficacy of RK-4 in patients with LHI by the proportion of NIHSS score improvement of >=8 points from baseline on the 14th +/-1 day of treatment

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

治疗第14+/-1天NIHSS评分较基线改善>=4分的比例

指标类型：

次要指标

Outcome：

Evaluate the efficacy of RK-4 in patients with LHI by the proportion of NIHSS score improvement of >=4 points from baseline on the 14th +/-1 day of treatment

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

治疗第4+/-1天、8+/-1天、14+/-1天NIHSS评分较基线的变化

指标类型：

次要指标

Outcome：

The changes of NIHSS scores from baseline on the 4th +/-1 day, 8th +/-1 day, and 14th +/-1 day of treatment

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

 使用后销毁  

说明

Fate of sample：

Destruction after use  

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 81 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）：

受试者筛选合格后，由研究者登录随机系统，获取受试者入组编号。受试者编号由字母“A”或“B”或“C”+研究中心序号（2位）+入组序号（2位）组成，A代表低剂量组，B代表中剂量组，C代表高剂量组，如A0101，A0102，B0101，…等

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

After the subjects are qualified,the researchers logged into the random system to obtain the enrollment numbers of the subjects.The subject number is composed of the letters "A", "B" or "C" + the research center number (2 digits) + the enrollment number (2 digits). A represents the low-dose group, B represents the medium-dose group, and C represents the high-dose group, such as A0101, A0102, B0101, etc.

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：

开放标签

Blinding：

Open Tag

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：

采用电子数据采集系统（EDC）进行数据的采集和管理

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

The Electronic Data Acquisition system (EDC) is adopted for data collection and management

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2025-09-30 15:51:00