ChiCTR2500104314 版本V1.0 版本创建时间2025/06/15 22:16:37 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：

 ChiCTR2500104314 

最近更新日期：

Date of Last Refreshed on：

 2025-06-15 22:16:33 

注册时间：

Date of Registration：

 2025-06-15 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

替妥尤单抗N01注射液在MRI显示明显眼外肌炎症但CAS评分为静止期的甲状腺眼病受试者中的疗效和安全性

Public title：

Efficacy and Safety of Teprotumumab N01 Injection in Subjects with Thyroid Eye Disease Exhibiting Significant Extraocular Muscle Inflammation on MRI but with CAS Scores in the Inactive Phase

注册题目简写：

English Acronym：

研究课题的正式科学名称：

替妥尤单抗N01注射液在MRI显示明显眼外肌炎症但CAS评分为静止期的甲状腺眼病受试者中的疗效和安全性

Scientific title：

Efficacy and Safety of Teprotumumab N01 Injection in Subjects with Thyroid Eye Disease Exhibiting Significant Extraocular Muscle Inflammation on MRI but with CAS Scores in the Inactive Phase

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：

邬易 

研究负责人：

何为民 

Applicant：

Yi Wu 

Study leader：

Weimin He 

申请注册联系人电话：

Applicant telephone：

 +86 147 2617 2930

研究负责人电话：

Study leader's
telephone：

+86 189 8060 1753

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：

 wuyitouk@163.com

研究负责人电子邮件：

Study leader's E-mail：

 hewm888@hotmail.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：

中国四川省成都市武侯区国学巷37号

研究负责人通讯地址：

中国四川省成都市武侯区国学巷37号

Applicant address：

No.37 Guoxue Lane, Wuhou District, Chengdu, Sichuan Province, China

Study leader's address：

No.37 Guoxue Lane, Wuhou District, Chengdu, Sichuan Province, China

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：

四川大学华西医院眼科

Applicant's institution：

Department of Ophthalmology, West China Hospital, Sichuan University

研究负责人所在单位：

四川大学华西医院眼科

Affiliation of the Leader：

Department of Ophthalmology, West China Hospital, Sichuan 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：

 2025年审(789)号

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：

四川大学华西医院生物医学伦理审查委员会

Name of the ethic committee：

Biomedical Ethics Review Committee, West China Hospital, Sichuan University

伦理委员会批准日期：

Date of approved by ethic committee：

 2025-05-16 00:00:00

伦理委员会联系人：

陈诗琦

Contact Name of the ethic committee：

Shiqi Chen

伦理委员会联系地址：

中国四川省成都市武侯区国学巷37号八角亭2105

Contact Address of the ethic committee：

2105 Bajiao Pavilion, No.37 Guoxue Lane, Wuhou District, Chengdu, Sichuan Province, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 85422654

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：

四川大学华西医院眼科

Primary sponsor：

Department of Ophthalmology, West China Hospital, Sichuan University

研究实施负责（组长）单位地址：

中国四川省成都市武侯区国学巷37号

Primary sponsor's address：

No.37 Guoxue Lane, Wuhou District, Chengdu, Sichuan Province, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

四川省

市(区县)：

Country：

China

Province：

Sichuan

City：

单位(医院)：

四川大学华西医院眼科

具体地址：

中国四川省成都市武侯区国学巷37号

Institution
hospital：

Department of Ophthalmology, West China Hospital, Sichuan University

Address：

No.37 Guoxue Lane, Wuhou District, Chengdu, Sichuan Province, China

经费或物资来源：

信达生物制药（苏州）有限公司

Source(s) of funding：

Innovent Biologics (Suzhou)

研究疾病：

甲状腺眼病  

Target disease：

Thyroid Eye Disease

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：

 其它 

Study phase：

N/A

研究设计：

单臂 

Study design：

Single arm 

研究目的：

1.主要目的：评估替妥尤单克隆抗体注射液在MRI显示明显眼外肌炎症但CAS评分为静止期的甲状腺眼病（Thyroid eye disease, TED）受试者中对眼外肌炎症的疗效，即MRI上眼外肌信号强度、眼外肌体积的变化。 2.次要目的： （1）评估替妥尤单克隆抗体注射液改善复视和眼球运动的疗效。 （2）评估替妥尤单克隆抗体注射液对Graves眼病-生活质量（Graves’ Ophthalmopathy Quality of Life, GO-QoL）问卷总分的影响。 （3）评估甲状腺眼病受试者静脉输注替妥尤单克隆抗体注射液的安全性和耐受性。  

Objectives of Study：

1. Primary Objective: To evaluate the efficacy of Teprotumumab in reducing extraocular muscle inflammation, as measured by changes in MRI signal intensity and muscle volume, in Thyroid Eye Disease (TED) subjects who show significant extraocular muscle inflammation on MRI but have a Clinical Activity Score (CAS) indicative of an inactive phase. 2. Secondary Objectives: (1) To evaluate the efficacy of Teprotumumab in improving diplopia and ocular motility. (2) To assess the impact of Teprotumumab on the total score of the Graves’ Ophthalmopathy Quality of Life (GO-QoL) questionnaire. (3) To evaluate the safety and tolerability of Teprotumumab in TED subjects.

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. 自愿参加研究并签署知情同意书 2. 筛选时年龄在18~80周岁（含）之间的男性或女性受试者 3. 筛选前被诊断为甲状腺眼病，且患眼CAS评分＜3 4. 行眼眶增强MRI，显示至少一条眼外直肌（下直肌、上直肌、内直肌、外直肌）明显炎症，满足以下条件：（1） T2WI上眼外肌信号强度增高，满足（受累眼外肌信号强度-颞肌信号强度）/颞肌信号强度（SIR）评分平均>=1.6分（采用赋分法， SIR＜30% 1分，30%<=SIR＜60% 2分，SIR>=60% 3分)；（2）T1WI增强扫描脂肪抑制序列上眼外肌信号强度明显强化，满足（受累眼外肌信号强度-颞肌信号强度）/颞肌信号强度（SIR）评分平均>=1.5分（采用赋分法， SIR＜30% 1分，30%≤SIR＜60% 2分，SIR>=60% 3分)；（3）冠状位上眼外肌最大增粗部位横截面积增大，以横截面积增大最多的肌肉为准，下直肌＞0.73mm^2，上直肌＞0.72mm^2，内直肌＞0.66mm^2，外直肌＞0.74 mm^2 5. 基线前未接受且在研究期间没有计划接受任何针对甲状腺眼病的治疗，包括药物治疗(局部或全身糖皮质激素、传统免疫抑制剂及其它生物制剂)、眼眶放射治疗、或手术治疗（眶减压术、斜视手术和眼睑退缩矫正术）等 6. 筛选时甲状腺功能正常，或有轻度甲状腺功能亢进或减退（定义为游离四碘甲腺原氨酸[FT4]和游离三碘甲腺原氨酸[FT3]水平偏离当地研究中心实验室正常参考范围50%以下），并及时纠正轻度甲状腺功能减退或甲状腺功能亢进，在临床试验期间保持甲状腺功能正常 7. 若为女性受试者，应是无生育能力或筛选期血妊娠试验阴性的并同意自筛选期至末次用药后120天内采取避孕措施的有生育能力女性；若为男性受试者，应同意自筛选期至末次用药后120天内采取避孕措施

Inclusion criteria

1. Voluntarily participate in the study and sign the informed consent form 2. Male or female subjects aged between 18~80 years old (inclusive) at screening 3. Diagnosed with thyroid ophthalmopathy before screening, and the CAS score of the affected eye is <3 4. Orbital MRI was performed with contrast, showing obvious inflammation of at least one extraocular rectus muscle (inferior rectus, superior rectus, medial rectus, lateral rectus muscle), and the following conditions were met: (1) the signal intensity of the extraocular muscle on T2WI was increased, and the average score of the temporal muscle signal intensity (SIR) was >=1.6 points (using the scoring method, SIR<30% 1 point, 30%<=SIR<60% 2 points, and the SIR was >= 60% 3 points); (2) The signal intensity of extraocular muscles was significantly enhanced on the fat inhibition sequence of T1WI enhanced scanning, and the average score of (involved extraocular muscle signal intensity-temporal muscle signal intensity)/temporal muscle signal intensity (SIR) score was >=1.5 points (using the assignment method, SIR< 30% 1 point, 30%≤ SIR<60% 2 points, SIR >= 60% 3 points); (3) The cross-sectional area of the maximum thickening part of the extraocular muscle in the coronal position increased, and the muscle with the largest increase in cross-sectional area was subject to the muscle with the largest increase in cross-sectional area, the > of the inferior rectus muscle was 0.73 mm^2, the superior rectus muscle > was 0.72 mm^2, the medial rectus muscle > was 0.66 mm^2, and the lateral rectus muscle > was 0.74 mm^2 5. Have not received and have not planned to receive any treatment for thyroid eye disease before baseline and have no plans to receive during the study period, including drug therapy (topical or systemic glucocorticoids, traditional immunosuppressants and other biological agents), orbital radiation therapy, or surgical treatment (orbital decompression, strabismus surgery and eyelid retraction correction), etc 6. Normal thyroid function at screening, or mild hyperthyroidism or hypothyroidism (defined as free tetraiodothyronine [FT4] and free triiodothyronine [FT3] levels deviating from the normal reference range of the local research center laboratory by less than 50%), and timely correction of mild hypothyroidism or hyperthyroidism, and maintenance of normal thyroid function during the clinical trial 7. If it is a female subject, it should be a female of childbearing potential who is of no childbearing potential or has a negative blood pregnancy test during the screening period and agrees to take contraceptive measures within 120 days from the screening period to the last dose; In the case of male subjects, they should agree to use contraception from the screening period until 120 days after the last dose

排除标准：

1.治疗前CAS较筛选时升高2分 2.由于视神经病变引起的最佳矫正视力下降，定义为过去6个月内视力下降两行、新的视野缺陷或继发于视神经受累的色觉损害 3.存在MRI禁忌症：包括绝对禁忌症（心脏起博器、人工耳蜗患者；心脏支架、人工瓣膜置换术后患者；体内有铁磁性血管夹者；眼球内有金属异物者）及相对禁忌症（扫描野内或附近含有铁磁性物品；有金属假牙者不能做鼻咽、口腔检查；体内有金属药泵者忌行相应部位检查；有宫内节育器者不能做盆腔检查；幽闭恐惧症病人；不能平卧30分钟以上、神志不清、严重缺氧、烦躁不安需要抢救的病人） 4. 先前存在任何其他疾病、代谢障碍、体格检查或临床实验室检查结果异常，有理由怀疑可能存在导致禁忌使用试验药物、或影响研究结果的解释、或使受试者处于治疗并发症高风险的疾病或状况，包括但不限于：确诊或临床疑似诊断的炎症性肠病、凝血功能障碍、筛选前6个月的脑血管意外或短暂性脑缺血或急性心肌梗死或不稳定性心绞痛或冠状动脉旁路移植术或经皮冠脉介入术（诊断性血管造影除外）或严重心律失常、过去5年内治疗过或未经治疗的恶性肿瘤病史（已成功切除并且无转移证据的皮肤鳞状细胞癌，基底细胞癌或局部宫颈原位癌者除外）、严重的全身感染、非TED导致的突眼等 5.筛选期任一耳存在：耳鸣或其他听力受损病史；或纯音测听结果异常（定义为0.5124kHz平均骨导听阈≥25dB或任一频率下骨导听阈>=40dB） 6.筛选时，存在控制不佳的糖尿病（定义为筛选时糖化血红蛋白>=9.0%，或在筛查前60天内有新的糖尿病药物[口服或注射]或目前处方的糖尿病药物剂量变化＞10%） 7.筛选时控制不佳的高血压，收缩压>=160 mmHg 或舒张压>=100 mmHg；或筛选前30天内调整降压药物（剂量或药物种类）；肾动脉狭窄，或不稳定性血压（包括体位性低血压等）的证据 8.筛选时12导联 ECG显示心率＜50 次/分或＞100 次/分，ECG 提示活动性心脏疾病，或研究者认为筛选时的ECG异常会干扰后续随访过程中对ECG结果的解释，尤其要排除QTcF＞450 ms（男），QTcF＞470 ms（女） 9. 筛选时，天门冬氨酸氨基转移酶（AST）或丙氨酸氨基转移酶（ALT）＞3倍ULN，或伴有活动性乙型肝炎（定义为HBsAg阳性 且伴有HBV-DNA载量大于1000 IU/mL者），或正在接受抗乙型肝炎病毒治疗 10.筛选时，肾小球滤过率（Glomerular Filtration Rate, GFR）＜30 ml/min/1.73m^2（应用MDRD公式：GFR =186×血肌酐（mg/dl）- 1.154×（年龄）-0.203×（0.742 [如果为女性]），血肌酐的单位换算：1 μmol/L=0.0113 mg/dL） 11. HIV抗体或HCV抗体阳性者或活动性梅毒者（定义为梅毒非特异性抗体阳性或经感染科会诊需要抗梅毒治疗者） 12.筛选前30天内，因非TED使用糖皮质激素者，局部使用（外用、鼻内、吸入）除外 13.筛选前60天对任何其他疾病使用研究药物或在试验过程中预期使用研究药物 14.筛选前90天内参加过其他干预性临床试验（如为药物，在其5个半衰期内，以更长者为准；维生素和矿物质除外），或者在研究期间试图参加其他临床试验 15.处于妊娠、哺乳期的女性受试者 16.筛选前2年有药物或酒精滥用史（根据研究者或患者报告） 17.已知的对于研究药物成分过敏者，或既往存在对其他单克隆抗体过敏者 18.研究者认为由于其他原因不适合参加本临床试验者

Exclusion criteria：

1. An increase of 2 points in Clinical Activity Score (CAS) from screening to baseline. 2.Best-corrected visual acuity (BCVA) decline due to optic neuropathy, defined as a two-line decrease in vision over the past 6 months, new visual field defects, or color vision impairment secondary to optic nerve involvement. 3.Contraindications to MRI, including absolute contraindications (e.g., pacemakers, cochlear implants; patients with cardiac stents or prosthetic heart valves; presence of ferromagnetic vascular clips; intraocular metallic foreign bodies) and relative contraindications (e.g., ferromagnetic objects within or near the scanning field; metallic dental prostheses precluding nasopharyngeal/oral examination; metallic infusion pumps contraindicating scans of the corresponding area; intrauterine devices precluding pelvic scans; claustrophobia; inability to lie flat for more than 30 minutes; impaired consciousness, severe hypoxia, agitation, or in need of emergency care). 4.Any pre-existing disease, metabolic disorder, abnormal findings on physical examination or clinical laboratory tests that, in the opinion of the investigator, may contraindicate the use of the investigational drug, interfere with interpretation of the study results, or pose a high risk of complications. These include but are not limited to: confirmed or suspected inflammatory bowel disease, coagulation disorders, cerebrovascular accident or transient ischemic attack within 6 months prior to screening, acute myocardial infarction, unstable angina, coronary artery bypass grafting, percutaneous coronary intervention (excluding diagnostic angiography), severe arrhythmias, history of malignancy within the past 5 years (excluding successfully resected and non-metastatic squamous cell carcinoma of the skin, basal cell carcinoma, or in situ carcinoma of the cervix), severe systemic infections, and proptosis not related to TED. 5.Presence of tinnitus or history of other hearing impairment in either ear during screening, or abnormal pure-tone audiometry (defined as an average bone conduction threshold ≥25 dB at 0.5–1–2–4 kHz, or >=40 dB at any single frequency). 6.Poorly controlled diabetes at screening, defined as hemoglobin A1c (HbA1c) >=9.0%, or initiation of a new diabetes medication (oral or injectable), or dose change >10% of a current diabetes medication within 60 days prior to screening. 7.Poorly controlled hypertension at screening, defined as systolic blood pressure >=160 mmHg or diastolic blood pressure >=100 mmHg; or changes in antihypertensive medication (dosage or type) within 30 days before screening; or evidence of renal artery stenosis or unstable blood pressure (including orthostatic hypotension). 8.Screening 12-lead ECG showing heart rate <50 bpm or >100 bpm, evidence of active cardiac disease, or ECG abnormalities that, in the investigator’s opinion, may interfere with interpretation during follow-up. Subjects with QTcF >450 ms (males) or >470 ms (females) should be excluded. 9.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3× upper limit of normal (ULN) at screening, or active hepatitis B infection (defined as positive HBsAg with HBV DNA >1000 IU/mL), or receiving antiviral treatment for hepatitis B. 10.Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2 at screening, calculated by the MDRD formula: GFR = 186 × (serum creatinine in mg/dL)^–1.154 × (age)^–0.203 × 0.742 (if female). Conversion: 1 μmol/L = 0.0113 mg/dL. 11.Positive HIV antibody or HCV antibody, or active syphilis (defined as a positive non-treponemal test or requiring anti-syphilitic treatment upon consultation with infectious disease specialists). 12.Use of glucocorticoids within 30 days prior to screening for non-TED indications, excluding topical, intranasal, or inhaled formulations. 13. Use of investigational drugs for other diseases within 60 days prior to screening or planned use during the study. 14. Participation in other interventional clinical trials within 90 days prior to screening (for investigational drugs, the longer of 90 days or 5 half-lives applies; vitamins and minerals are excluded), or intention to participate in other clinical trials during the study period. 15.Female subjects who are pregnant or breastfeeding. 16. History of drug or alcohol abuse within 2 years prior to screening (based on investigator judgment or subject self-report). 17. Known hypersensitivity to components of the investigational drug, or history of allergy to other monoclonal antibodies. 18. Any other condition which, in the opinion of the investigator, renders the subject unsuitable for participation in the clinical trial.

研究实施时间：

Study execute time：

从 From 2025-06-20 00:00:00至 To 2026-07-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-06-20 00:00:00 至 To 2025-07-31 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 15

Group：

Experimental group

Sample size：

干预措施：

替妥尤单抗治疗

干预措施代码：

Intervention：

Tetumumab treatment

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 四川省 

市(区县)：

  

Country：

China

Province：

Sichuan

City：

单位(医院)：

 四川大学华西医院眼科 

单位级别：

 三甲 

Institution
hospital：

Department of Ophthalmology, West China Hospital, Sichuan University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

MRI上受累眼外肌信号强度比（SIR）

指标类型：

主要指标

Outcome：

Signal intensity ratio (SIR) of the affected extraocular muscles on MRI

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

MRI上受累眼外肌体积

指标类型：

主要指标

Outcome：

Volume of the affected extraocular muscles on MRI

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

复视评分

指标类型：

次要指标

Outcome：

Diplopia Score

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

眼球运动

指标类型：

次要指标

Outcome：

Eye movement

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

安全性

指标类型：

次要指标

Outcome：

Safety

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

 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 80 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：

无

Blinding：

None

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

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：

CRF

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

CRF

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：

  2025-06-15 22:16:33