ChiCTR2600127018 版本V1.0 版本创建时间2026/06/23 09:45:03 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：

ChiCTR2600127018 

最近更新日期：

Date of Last Refreshed on：

2026-06-23 09:42:06 

注册时间：

Date of Registration：

2026-06-23 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

低剂量贝林妥欧单抗治疗难治性自身免疫性脑炎和自身免疫性小脑炎的有效性与安全性研究

Public title：

Efficacy and Safety of Low-Dose Blinatumomab in the Treatment of Refractory Autoimmune Encephalitis and Autoimmune Cerebellitis

注册题目简写：

English Acronym：

研究课题的正式科学名称：

低剂量贝林妥欧单抗治疗难治性自身免疫性脑炎的有效性与安全性研究

Scientific title：

Efficacy and Safety of Low-Dose Blinatumomab in the Treatment of Refractory Autoimmune Encephalitis

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：

徐望舒 

研究负责人：

徐望舒 

Applicant：

Wangshu Xu 

Study leader：

Wangshu Xu 

申请注册联系人电话：

Applicant telephone：

+86 13621017376

研究负责人电话：

Study leader's telephone：

+86 10 59978366

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：

xuwangshu@mail.ccmu.edu.cn

研究负责人电子邮件：

Study leader's E-mail：

xws921@sina.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：

北京市丰台区南四环西路119号

研究负责人通讯地址：

北京市丰台区南四环西路119号

Applicant address：

119 South 4th Ring Road West, Fengtai District, Beijing

Study leader's address：

119 South 4th Ring Road West, Fengtai District, Beijingg

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：

首都医科大学附属北京天坛医院

Applicant's institution：

Beijing Tiantan Hospital, Capital Medical University

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/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

KY2026-016-02, KY2026-016-03

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医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Beijing Tiantan Hospital Affiliated to Capital Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

2026-04-21 00:00:00

伦理委员会联系人：

梁晓珊

Contact Name of the ethic committee：

Liang Xiaoshan

伦理委员会联系地址：

北京市丰台区南四环西路119号

Contact Address of the ethic committee：

119 South 4th Ring Road West, Fengtai District, Beijing

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 10 59975692

伦理委员会联系人邮箱：

Contact email of the ethic committee：

liangxiaoshan127@126.com

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：

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)：

北京市

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

具体地址：

北京市丰台区南四环西路119号

Institution
hospital：

Beijing Tiantan Hospital, Capital Medical University

Address：

119 South 4th Ring Road West, Fengtai District, Beijing

经费或物资来源：

自选课题（自筹）

Source(s) of funding：

Self-raised

Target disease：

Refractory Autoimmune Encephalitis, Refractory Autoimmune Cerebellitis

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 上市后药物 

Study phase：

4

研究设计：

单臂 

Study design：

Single arm 

研究目的：

主要目的：探索低剂量贝林妥欧单抗在难治性抗体阳性自身免疫性脑炎和自身免疫性小脑炎患者中的临床疗效和安全性。 次要目的： （1）观察不同抗体类型患者和自身免疫性小脑炎对治疗的应答差异； （2）初步评估贝林妥欧单抗对B细胞活化、抗体滴度、免疫指标的影响。  

Objectives of Study：

Primary Objective: To explore the clinical efficacy and safety of low-dose blinatumomab in patients with refractory antibody-positive autoimmune encephalitis and autoimmune cerebellitis. Secondary Objectives: (1) To observe the differences in treatment response among patients with different antibody subtypes and those with autoimmune cerebellitis; (2) To preliminarily evaluate the effects of blinatumomab on B cell activation, antibody titers and immune indicators.

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.发病年龄≥18岁，男女不限； 2.诊断明确的抗体阳性自身免疫性脑炎和自身免疫性小脑炎； 3.难治性AE为明确的抗体阳性AE及ACA且满足以下标准的受试者： 基线时测得mRS评分稳定（至少24小时）为>3分。 在基线访视前超过6周以上接受了首次急性一线治疗。 急性一线治疗定义为，至少持续3天的甲基强的松龙（IV，≥500mg/天）（或口服糖皮质激素给药等效物），和/或至少持续3天的 IVIG 治疗和/或 PE，或上述任何组合用药。 接受了首个急性一线治疗疗程之外的免疫治疗，必须满足以下标准: （1） 对于接受利妥昔单抗的受试者，至少在筛选前2个月开始治疗疗程、至少在随机化前4周进行最后一次给药，并且在基线访视前4周内mRS评分2个月没有改善. （2）对于接受其他IST（即，吗替麦考酚酯、环磷酰胺或硫唑嘌呤等）4周治疗的受试者，在筛选前至少治疗2个月、剂量在筛选前至少4周内保持稳定，以及mRS评分在基线访视前4周内无改善. （3） 对于接受口服激素的受试者，每日接受>20mg稳定剂量的泼尼松龙（或其等效物）的、激素剂量在筛选前4周内无增加，以及mRS评分在基线访视前4周内无改善. （4）对于接受急性一线治疗重复疗程的受试者，必须在基线访视前≥2周完成治疗。 4.入组前对于接受口服糖皮质激素治疗的受试者，每日接受≥20mg稳定计量泼尼松（或其他等效物）的、类固醇剂量在入组前4周内无增加，且mRS评分在入组前4周内无改善；对于接受利妥昔治疗的受试者，至少在入组前2个月开始治疗疗程，至少在入组前4周进行最后1次给药，且入组前4周之内mRS评分没有改善；对于接受其他免疫抑制剂（如硫唑嘌呤、霉酚酸酯等）的受试者，入组前至少治疗2个月、剂量在入组前至少4周内保持稳定，且mRS评分在入组前4周内无改善；对于接受急性一线治疗重复疗程的受试者，必须在入组前≥2周完成治疗。 5.患者本人及/授权亲属家属知情同意并签署知情同意书。 6.对于有生育潜能的女性：同意在治疗期间以及接受末次给药后至少3个月内保持禁欲（避免异性性交）或采用适当的避孕措施。月经初潮后，尚未达到绝经后状态（≥12 个月连续性闭经，除绝经外无其他原因），且未因手术（即，切除卵巢、输卵管和/或子宫）或研究者确定的其他原因（例如，Müllerian发育不全）而永久不孕的女性均被视为有生育潜能。为与当地指南或规定保持一致，可适当调整有生育潜能的定义。

Inclusion criteria

1.Aged at onset >= 18 years, male and female eligible. 2.Definite diagnosis of antibody-positive autoimmune encephalitis and autoimmune cerebellitis; 3.Subjects with definite antibody-positive autoimmune encephalitis (AE) and autoimmune cerebellitis (ACA) who meet the following criteria are defined as having refractory AE: A stable modified Rankin Scale (mRS) score > 3 measured at baseline for at least 24 hours. Received the first-line acute treatment more than 6 weeks prior to the baseline visit. First-line acute treatment is defined as: Methylprednisolone intravenous infusion (IV) at a dose of >=500 mg/day for at least 3 consecutive days (or equivalent oral glucocorticoid), and/or intravenous immunoglobulin (IVIG) therapy for at least 3 consecutive days, and/or plasma exchange (PE), or any combination of the above regimens. Subjects have received additional immunotherapy beyond the initial course of first-line acute treatment, and must meet one of the following criteria: (1) For subjects receiving rituximab: the treatment course was initiated at least 2 months prior to screening, the last administration was given at least 4 weeks before randomization, and no improvement in mRS score was observed within 2 months prior to the baseline visit. (2) For subjects receiving other immunosuppressive therapy (IST), including mycophenolate mofetil, cyclophosphamide, azathioprine, etc., for a 4-week treatment period: treatment duration of at least 2 months before screening with a stable dose maintained for at least 4 weeks prior to screening, and no improvement in mRS score within 4 weeks before the baseline visit. (3) For subjects on oral glucocorticoids: receiving a stable daily dose of prednisolone >20 mg (or equivalent), with no dose increase within 4 weeks prior to screening, and no improvement in mRS score within 4 weeks before the baseline visit. (4) For subjects receiving a repeated course of first-line acute treatment: the repeated course must be completed ≥ 2 weeks prior to the baseline visit. 4.Before enrollment: For subjects receiving oral glucocorticoid therapy: receiving a stable daily dose of >= 20 mg prednisone (or other equivalents), with no increase in steroid dose within 4 weeks before enrollment, and no improvement in mRS score within 4 weeks before enrollment. For subjects receiving rituximab therapy: the treatment course was initiated at least 2 months before enrollment, the last administration was given at least 4 weeks before enrollment, and no improvement in mRS score was observed within 4 weeks before enrollment. For subjects receiving other immunosuppressants (such as azathioprine, mycophenolate mofetil, etc.): treatment duration of at least 2 months before enrollment, with a stable dose maintained for at least 4 weeks prior to enrollment, and no improvement in mRS score within 4 weeks before enrollment. For subjects receiving a repeated course of first-line acute treatment: the repeated course must be completed >= 2 weeks before enrollment. 5.The patient himself/herself and/or his/her authorized relatives/family members have been fully informed, consented and signed the informed consent form. 6.For females of childbearing potential: Agree to practice abstinence (avoid heterosexual intercourse) or use appropriate contraceptive measures during treatment and for at least 3 months after the last administration. Females who have had menarche, have not yet reached a postmenopausal state (>= 12 consecutive months of amenorrhea with no other causes except menopause), and are not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or other causes determined by the investigator (e.g., Müllerian agenesis) are considered to have childbearing potential. To be consistent with local guidelines or regulations, the definition of childbearing potential may be appropriately adjusted.

排除标准：

1.存在系统性肿瘤及中枢神经系统肿瘤，如大脑胶质瘤病等或既往癌症史（卵巢或卵巢外畸胎瘤,也称皮样囊肿、生殖细胞肿瘤、皮肤鳞状细胞癌或皮肤基底细胞癌除外）鳞状细胞癌和基底细胞癌的治疗应有记录显示，在随机分组前3个月以上已成功治愈；遗传性疾病，如线粒体脑病等；神经系统变性病，如路易体痴呆等；既往存在癫痫病史，目前仍有癫痫发作严重颅脑创伤如车祸等；代谢性与中毒性脑病，如Wernicke脑病等；
2.感染性疾病，如病毒性脑炎等；筛查前一周内患有活动性感染或无法控制的感染，需要进行全身治疗；有严重反复或慢性感染史，尤其是有呼吸系统疾病的反复或慢性感染史；
3.筛查时确诊乙型肝炎血清学阳性（乙型肝炎表面抗原和核心抗原）和/或丙型肝炎PCR阳性。
4.筛查时确诊有活动性结核；
5.患有其他长期服用糖皮质激素或免疫抑制剂的疾病；
6.已知有原发性免疫缺陷（先天性或获得性）病史或潜在疾病，如人类免疫缺陷病毒（HIV）感染或脾切除术，使参与者易受感染。
7.筛选前三个月内接受过实体器官移植或造血干细胞移植；
8.入组前 3 周内接种过任何活疫苗或减毒疫苗（灭活疫苗亦可接受）。 入组前1年内接种过卡介苗。
9.先天性心脏病或筛查前 6 个月内有急性心肌梗死病史，或严重心律失常（包括多形性室性心动过速、室性心动过速等）；或合并中度至大量心包积液、严重心肌炎等；或生命体征不稳定，需要使用升压药物维持血压的患者；或左心室射血分数（LVEF）≤ 55%，明显心电图异常。
10.实验室指标有以下任意一项 绝对淋巴细胞计数（ALC）≤0.5×10?/L 绝对中性粒细胞计数（ANC）≤ 0.5×10?/L 免疫球蛋白 G 水平低于下限（≤5.0 克/升） CD4 T 淋巴细胞计数 < 300 个细胞/μL 血红蛋白≤80g/L。 血小板计数≤75×10?/L 肾小球滤过率 (eGFR) ≤ 30 mL/min/1.73m2。 天冬氨酸转氨酶 (AST) 和丙氨酸转氨酶 (ALT) ≥ 3 ×正常值上限(ULN)；总胆红素 ≥ 2 ×正常值上限(ULN)。
11.正处于妊娠期或哺乳期的女性及试验期间有生育计划的患者；
12.医疗记录不完整及拒绝参与登记调查者；
13.已知对试验药物制剂的任何成分有过敏或反应史，或对任何生物治疗有过敏反应史。

Exclusion criteria：

1.There are systemic tumors and central nervous system tumors, such as cerebral gliomatosis, or a past history of cancer (excluding ovarian or extraovarian teratomas, also known as dermoid cysts, germ cell tumors, cutaneous squamous cell carcinoma, or cutaneous basal cell carcinoma); for squamous cell carcinoma and basal cell carcinoma, there should be records showing that they have been successfully cured for more than 3 months before randomization; hereditary diseases, such as mitochondrial encephalopathy; neurodegenerative diseases of the nervous system, such as Lewy body dementia; a past history of epilepsy with ongoing epileptic seizures; severe craniocerebral trauma, such as traffic accidents; metabolic and toxic encephalopathy, such as Wernicke encephalopathy. 2.Infectious diseases, such as viral encephalitis, etc.; having active infections requiring systemic treatment within one week before screening, or a history of severe recurrent or chronic infections, especially a history of recurrent or chronic infections related to respiratory diseases. 3.Serologically confirmed positive hepatitis B (hepatitis B surface antigen and hepatitis B core antibody) and/or positive hepatitis C PCR at screening. 4.Confirmed active tuberculosis at screening. 5.Having other diseases requiring long-term use of glucocorticoids or immunosuppressive agents. 6.Known history or underlying conditions of primary immunodeficiency (congenital or acquired), such as human immunodeficiency virus (HIV) infection or splenectomy, which render the participant susceptible to infection. 7.Having received solid organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening. 8.Receipt of any live or attenuated vaccine within 3 weeks prior to enrollment (inactivated vaccines are permitted). Receipt of Bacillus Calmette?Guérin (BCG) vaccine within 1 year prior to enrollment. 9.Patients with congenital heart disease, or a history of acute myocardial infarction within 6 months prior to screening, or severe arrhythmia (including polymorphic ventricular tachycardia, ventricular tachycardia, etc.); those complicated with moderate to large pericardial effusion, severe myocarditis, etc.; those with unstable vital signs requiring vasopressor agents to maintain blood pressure; or those with left ventricular ejection fraction (LVEF) <= 55% and significant abnormal electrocardiographic findings. 10.Any one of the following abnormal laboratory parameters: Absolute lymphocyte count (ALC) <= 0.5×10?/L; Absolute neutrophil count (ANC) <= 0.5×10?/L; Immunoglobulin G level below the lower limit of normal (<= 5.0 g/L); CD4 T-lymphocyte count < 300 cells/μL; Hemoglobin <= 80 g/L; Platelet count <= 75×10?/L; Estimated glomerular filtration rate (eGFR) <= 30 mL/min/1.73m2; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >= 3 × upper limit of normal (ULN); total bilirubin >= 2 × upper limit of normal (ULN). 11.Females who are pregnant or breastfeeding, as well as those planning to become pregnant during the trial period. 12.Patients with incomplete medical records or those who refuse to participate in registration and investigation. 13.Known history of allergy or adverse reaction to any ingredient of the investigational medicinal product, or history of hypersensitivity to any biological therapy.

研究实施时间：

Study execute time：

从 From 2026-01-01 00:00:00至 To 2028-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2026-06-24 00:00:00 至 To 2028-12-31 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

12

Group：

Experimental group

Sample size：

干预措施：

低剂量贝林妥欧单抗治疗 第一周期（第 1 周）：起始剂量 9μg/天，连续静脉输注 5 天（总剂量 45μg）； 第二周期（第 3 周）：再次重复给药，剂量、用法同第一周期。 如第三周 mRS 评分无下降同时外周血 B 细胞（CD3-/CD19+）比例仍未≤1%可 考虑计量优化为 15 μg/m2/day, 最大剂量 28 μg/day。

干预措施代码：

Intervention：

Low-dose blinatumomab treatment: Cycle 1 (Week 1): Starting dose of 9 μg/day, administered as a continuous intravenous infusion for 5 days (total dose: 45 μg). Cycle 2 (Week 3): The same dose and regimen as Cycle 1 were repeated. If at Week 3 the mRS score shows no decrease and the peripheral blood B?cell (CD3?/CD19+) proportion remains >1%, dose escalation to 15 μg/m2/day (maximum 28 μg/day) may be considered.

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 

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：

三级甲等 

Institution
hospital：

Beijing Tiantan Hospital, Capital Medical University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 北京市 

市(区县)：

  

Country：

China 

Province：

Beijing 

City：

 

单位(医院)：

北京朝阳中西医结合急诊抢救医院 

单位级别：

三级甲等 

Institution
hospital：

Beijing Chaoyang Hospital of Integrative Medicine for Emergency and Rescue

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 北京市 

市(区县)：

  

Country：

China 

Province：

Beijing 

City：

 

单位(医院)：

首都医科大学宣武医院 

单位级别：

三级甲等 

Institution
hospital：

Xuanwu Hospital, Capital Medical University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 四川省 

市(区县)：

  

Country：

China 

Province：

Sichuan 

City：

 

单位(医院)：

四川大学华西医院 

单位级别：

三级甲等 

Institution
hospital：

West China Hospital, Sichuan University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

改良 RANKIN 量表评分

指标类型：

主要指标

Outcome：

Modified Rankin Scale, mRS

Type：

Primary indicator

测量时间点：

第3周（±1天）、第4周（±1天）、第5周（±1天）、第6周（±1天）、第8周（±1天）、第12周（±1天）、第24周（±3天）、第36周（±5天）、第48周（±10天）

测量方法：

Measure time point of outcome：

Week 3 (±1 day), Week 4 (±1 day), Week 5 (±1 day), Week 6 (±1 day), Week 8 (±1 day), Week 12 (±1 day), Week 24 (±1 day), Week 36 (±1 day), Week 48 (±1 day),

Measure method：

指标中文名：

临床评估量表评分

指标类型：

主要指标

Outcome：

Clinical Assessment Scale for Autoimmune Encephalitis, CASE

Type：

Primary indicator

测量时间点：

第3周（±1天）、第4周（±1天）、第5周（±1天）、第6周（±1天）、第8周（±1天）、第12周（±1天）、第24周（±3天）、第36周（±5天）、第48周（±10天）

测量方法：

Measure time point of outcome：

Week 3 (±1 day), Week 4 (±1 day), Week 5 (±1 day), Week 6 (±1 day), Week 8 (±1 day), Week 12 (±1 day), Week 24 (±1 day), Week 36 (±1 day), Week 48 (±1 day),

Measure method：

指标中文名：

自身免疫性小脑炎需要额外评价国际合作共济失调评估量表

指标类型：

主要指标

Outcome：

International Cooperative Ataxia Rating Scale,ICARS

Type：

Primary indicator

测量时间点：

第3周（±1天）、第4周（±1天）、第5周（±1天）、第6周（±1天）、第8周（±1天）、第12周（±1天）、第24周（±3天）、第36周（±5天）、第48周（±10天）

测量方法：

Measure time point of outcome：

Week 3 (±1 day), Week 4 (±1 day), Week 5 (±1 day), Week 6 (±1 day), Week 8 (±1 day), Week 12 (±1 day), Week 24 (±1 day), Week 36 (±1 day), Week 48 (±1 day),

Measure method：

指标中文名：

蒙特利尔认知评估量表

指标类型：

次要指标

Outcome：

Montreal Cognitive Assessment, MoCA

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

简易精神状态检查量表

指标类型：

次要指标

Outcome：

Minimum Mental State Examination, MMSE

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

不良事件

指标类型：

次要指标

Outcome：

Adverse Events

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：

血清

组织：

Sample Name：

plasma

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation after use  

Note：

标本中文名：

脑脊液

组织：

Sample Name：

Cerebrospinal fluid

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation 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 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

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)：

No sharing

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；电子管理系统

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

Case Record Form, Electronic data capture

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2026-06-23 09:42:06