ChiCTR2100045296 版本V1.4 版本创建时间2021/11/16 05:35:05 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：

 ChiCTR2100045296 

最近更新日期：

Date of Last Refreshed on：

 2021-11-16 05:33:11 

注册时间：

Date of Registration：

 2021-04-10 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

PD-1抑制剂Tislelizumab联合HMA和阿糖胞苷治疗中高危骨髓增生异常综合征的临床研究

Public title：

The clinical study of PD-1 inhibitor Tislelizumab combined with HMA and cytarabine in the treatment of high-risk myelodysplastic syndromes

注册题目简写：

English Acronym：

研究课题的正式科学名称：

PD-1抑制剂Tislelizumab联合HMA和阿糖胞苷治疗中高危骨髓增生异常综合征的临床研究

Scientific title：

The clinical study of PD-1 inhibitor Tislelizumab combined with HMA and cytarabine in the treatment of high-risk myelodysplastic syndromes

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：

洪梅 

研究负责人：

洪梅 

Applicant：

Hong Mei 

Study leader：

Hong Mei 

申请注册联系人电话：

Applicant telephone：

 +86 13037137937

研究负责人电话：

Study leader's
telephone：

+86 13037137937

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：

 meihongcncn@aliyun.com

研究负责人电子邮件：

Study leader's E-mail：

 meihongcncn@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：

湖北省武汉市江汉区解放大道1227号

研究负责人通讯地址：

湖北省武汉市江汉区解放大道1227号

Applicant address：

1227 Jiefang Avenue, Jianghan District, Wuhan, Hubei

Study leader's address：

1227 Jiefang Avenue, Jianghan District, Wuhan, Hubei

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：

华中科技大学同济医学院附属协和医院

Applicant's institution：

Union Hospital, Tongji Medical College of HUST

研究负责人所在单位：

华中科技大学同济医学院附属协和医院

Affiliation of the Leader：

Union Hospital, Tongji Medical College of HUST

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：

 [2020]伦理字（0554）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：

华中科技大学同济医学院附属协和医院医学伦理委员会

Name of the ethic committee：

Ethics Committee of Union Hospital,Tongji Medical College, Huazhong University of Science and Technology

伦理委员会批准日期：

Date of approved by ethic committee：

 2020-11-10 00:00:00

伦理委员会联系人：

褚圆圆

Contact Name of the ethic committee：

Chu Yuanyuan

伦理委员会联系地址：

湖北省武汉市解放大道1227号

Contact Address of the ethic committee：

1227 Jiefang Avenue, Jianghan District, Wuhan, Hubei

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 27 85726375

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 whunionlunli@126.com

研究实施负责（组长）单位：

华中科技大学同济医学院附属协和医院血液科

Primary sponsor：

Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technol

研究实施负责（组长）单位地址：

湖北省武汉市江汉区解放大道1227号

Primary sponsor's address：

1227 Jiefang Avenue, Jianghan District, Wuhan, Hubei

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

市(区县)：

武汉

Country：

China

Province：

Hubei

City：

Wuhan

单位(医院)：

华中科技大学同济医学院附属协和医院

具体地址：

江汉区解放大道1227号

Institution
hospital：

Union Hospital, Tongji Medical College of HUST

Address：

1227 Jiefang Avenue, Jianghan District

经费或物资来源：

本项目的经费来源为自筹。

Source(s) of funding：

The source of funding for this project is self-raised.

研究疾病：

PD-1抑制剂Tislelizumab联合HMA和阿糖胞苷治疗中高危骨髓增生异常综合征的临床研究  

Target disease：

The clinical study of PD-1 inhibitor Tislelizumab combined with HMA and cytarabine in the treatment of high-risk myelodysplastic syndromes

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：

队列研究 

Study design：

Cohort study 

研究目的：

探索Tislelizumab联合HMA和阿糖胞苷方案在中高危MDS的安全性和有效性，尝试新的安全性可控、疗效更好的临床方案，使更多患者获益。  

Objectives of Study：

Explore the safety and effectiveness of Tislelizumab combined with HMA and cytarabine regimens in medium to high-risk MDS, and try new clinical regimens with controllable safety and better efficacy to benefit more patients.

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.男性或非妊娠非哺乳期女性患者，年龄≥18岁；
2.根据2016 WHO诊断标准（附件1）及IPSS-R预后评分（附件2），经骨髓穿刺或活检确诊的中高危（IPSS-R预后评分＞3.5）的MDS患者；
3.根据美国东部肿瘤协作组体力状态评分（ECOG PS，附件3）为0~2分；
4.不适合或拒绝接受强化疗及异基因造血干细胞移植（因年龄、合并症、没有合适供体等因素）；
5.未接受过去甲基化治疗或化疗的初诊MDS患者（允许输血、造血生长因子及补充造血原料治疗）；
6.具有充分的器官功能，定义如下：
1) 肝功能：血清总胆红素（TBIL）≤1.5×正常上限（ULN）；丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）≤2.5×ULN。白蛋白（ALB）＞30g/L。Gilbert综合征受试者要求TBIL≤3×ULN。
2) 肾功能：血清肌酐（Cr）≤1.5×ULN或内生肌酐清除率（CCr）≥50 ml/min（用CKD-EPI公式计算）。
3) 凝血功能：国际标准化比率（INR）≤1.5，且凝血酶原时间（PT）或活化部分凝血活酶时间（ APTT）≤1.5×ULN；
7.预期生存时间≥12周；
8.育龄期女性受试者或伴侣为育龄期妇女的男性受试者，需在整个治疗期及治疗期后6个月采取有效的避孕措施；
9.能够耐受在筛选期及检测时间点进行骨髓穿刺及活检检查；
10.签署书面知情同意书，而且能够遵守方案规定的访视及相关程序。

Inclusion criteria

1. Male or non-pregnant non-lactating female patients, aged >=18 years;
2. According to the 2016 WHO diagnostic criteria (Annex 1) and IPSS-R prognostic score (Annex 2), MDS patients with medium to high risk (IPSS-R prognostic score>3.5) diagnosed by bone marrow aspiration or biopsy;
3. According to the Eastern United States Oncology Group's physical status score (ECOG PS, Appendix 3), it is 0~2 points;
4. Not suitable or refuse to receive intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (due to factors such as age, comorbidities, lack of suitable donors, etc.);
5. Newly diagnosed MDS patients who have not received past methylation therapy or chemotherapy (allowing blood transfusion, hematopoietic growth factor and supplementary hematopoietic raw material treatment);
6. Has sufficient organ function, defined as follows:
1) Liver function: serum total bilirubin (TBIL) <= 1.5 x upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x ULN. Albumin (ALB) > 30g/L. Subjects with Gilbert syndrome require TBIL<=3×ULN.
2) Renal function: Serum creatinine (Cr) <= 1.5 x ULN or endogenous creatinine clearance (CCr) >= 50 ml/min (calculated with CKD-EPI formula).
3) Coagulation function: International normalized ratio (INR) <= 1.5, and prothrombin time (PT) or activated partial thromboplastin time (APTT) <= 1.5 x ULN;
7. Expected survival time >= 12 weeks;
8. Female subjects of childbearing age or male subjects whose partners are women of childbearing age must take effective contraceptive measures throughout the treatment period and 6 months after the treatment period;
9. Able to tolerate bone marrow aspiration and biopsy during the screening period and detection time point;
10. Sign a written informed consent and be able to comply with the visit and related procedures stipulated in the plan.

排除标准：

排除标准（一）：
1.MDS转化为AML的患者，定义为骨髓涂片中原始及幼稚细胞≥20%，或存在AML特征性的克隆性改变如t（15;17），t（8;21），t（16;16），inv（16）；
2.治疗相关的MDS（t-MDS）、骨髓增殖性疾病（Myeloproliferative Neoplasms, MPN）转化的MDS；
3.包括慢性粒单核细胞白血病在内的MDS/MPN（骨髓增生综合征/骨髓增殖性疾病）；
4. IPSS-R≤3.5分的MDS患者；
5.既往接受过针对MDS治疗的患者（包括去甲基化药物、细胞毒药物化疗、CAR-T、免疫检查点抑制剂等）；
6.既往曾暴露于任何抗PD-1单抗；
7.同时参与另一项干预性临床研究，除非参与观察性（非干预性）临床研究或处于干预性研究的生存随访阶段；
8.在首剂研究治疗之前7天之内使用过免疫抑制药物，不包括喷鼻、吸入性或其他途径的局部糖皮质激素或生理剂量的系统性糖皮质激素（即不超过10 mg/天泼尼松或等效剂量的其他糖皮质激素）。允许使用预防性的皮质类固醇以避免过敏反应（例如，静脉造影剂或化疗药物给药前预处理）；
排除标准（二）
9.在首剂研究治疗之前4周之内或计划在研究期间接受减毒活疫苗；
10.在首剂研究治疗之前4周之内接受过重大的外科手术（开颅、开胸或开腹手术）或者预期在研究治疗期间需要接受大手术（PICC术及深静脉置管术除外）；
11.入组前存在既往抗肿瘤治疗引起的未恢复至NCI CTCAE V5.0 0~1级的毒性；
12.活动性的未控制的凝血障碍，需要治疗性使用抗凝药物（如华法林、低分子肝素等）治疗的患者；
13.已知存在活动性或可疑的自身免疫性疾病或既往2年内的该病病史（在近2年之内不需系统治疗的白癜风、银屑病、桥本氏甲状腺炎或格雷夫氏病，仅需要甲状腺激素替代治疗的甲状腺功能减退以及仅需要胰岛素替代治疗的I型糖尿病受试者可以入组）；
14.已知原发性免疫缺陷病史；
15.已知患有活动性肺结核病史；
16.已知异体器官移植史和异体造血干细胞移植史；
排除标准（三）
17.未控制的并发性疾病包括但不限于：
1）HIV感染者（HIV抗体阳性）；
2）处于活动期或临床控制不佳的严重感染；
3）症状性充血性心力衰竭（纽约心脏病协会分级II~IV级）或症状性或控制不佳的心律失常；
4）即使给予规范治疗仍然未受控制的动脉高血压（收缩压≥160 mmHg或舒张压≥100 mmHg）；
5）在入选治疗前6个月内发生过任何动脉血栓栓塞事件，包括心肌梗死、不稳定型心绞痛、脑血管意外或一过性脑缺血发作；
6）需要立即干预的食管或胃静脉曲张（例如，绑扎或硬化治疗）或根据研究者的意见或咨询胃肠病学专家或肝脏病学专家认为其出血风险较高，有门静脉高压证据（包括影像学检查发现脾大）或既往有静脉曲张出血病史的受试者在入组前3个月内必须接受内镜评估；
7）在入选研究前6个月内有胃肠道穿孔和/或瘘管的病史；
8）在入选研究前6个月内发生任何危及生命的出血事件如颅内出血或需要输血、内镜或手术治疗的3或4级胃肠道/静脉曲张出血事件；
9）在入组前6个月内有深静脉血栓、肺栓塞或其它任何严重血栓栓塞的病史（植入式静脉输液港或导管源性血栓形成，或浅表静脉血栓形成不被视为“严重”血栓栓塞）；
10）不受控制的代谢紊乱或其它非恶性肿瘤器官或全身性疾病或癌症继发反应，并可导致较高医学风险和/或生存期评价不确定性；
11）肝性脑病、肝肾综合征或Child-Pugh B级或更为严重肝硬化；
12）肠梗阻或以下疾病的病史：炎性肠病或广泛肠切除（部分结肠切除或广泛小肠切除，并发慢性腹泻）、克罗恩氏病、溃疡性结肠炎或慢性腹泻；
13）可能会导致以下结果的其它急性或慢性疾病、精神疾病或实验室检测值异常：增加研究参与或研究药物给药的相关风险，或者干扰研究结果的解读，而且根据研究者的判断将受试者列为不符合参加本研究的资格。
14）急性或者慢性活动性乙型肝炎或丙型肝炎感染者：HBsAg阳性且乙型肝炎病毒（HBV）DNA＞200 IU/ml或1000拷贝/ml；丙型肝炎病毒（HCV）抗体阳性且RNA阳性。
排除标准（四）
18.其他原发性恶性肿瘤病史，除外：
1）已根治的恶性肿瘤，在入选研究之前≥5年无已知的活动性疾病并且复发的风险极低；
2）经充分治疗且无疾病复发证据的非黑色素瘤皮肤癌或恶性雀斑样痣；
3）经充分治疗且无疾病复发证据的原位癌。
19.妊娠或哺乳的女性受试者；
20.其他研究者认为不适合入组的情况。

Exclusion criteria：

Exclusion criteria (One):
1. Patients with MDS transformed into AML are defined as the original and immature cells in the bone marrow smear >= 20%, or the presence of AML characteristic clonal changes such as t(15;17), t(8;21), t(16 ;16), inv(16);
2. Treatment related MDS (t-MDS), myeloproliferative neoplasms (Myeloproliferative Neoplasms, MPN) transformed MDS;
3. MDS/MPN (myelodysplastic syndrome/myeloproliferative disease) including chronic myelomonocytic leukemia;
4. MDS patients with IPSS-R<=3.5 points;
5. Patients who have previously received treatment for MDS (including demethylation drugs, cytotoxic drug chemotherapy, CAR-T, immune checkpoint inhibitors, etc.);
6. Previous exposure to any anti-PD-1 monoclonal antibody;
7. Participate in another interventional clinical study at the same time, unless participating in an observational (non-interventional) clinical study or in the survival follow-up stage of an interventional study;
8. Have used immunosuppressive drugs within 7 days before the first dose of study treatment, excluding nasal spray, inhalation or other local glucocorticoids or physiological doses of systemic glucocorticoids (ie no more than 10 mg/day Prednisone or other glucocorticoids in equivalent doses). Prophylactic corticosteroids are allowed to avoid allergic reactions (for example, pretreatment before administration of intravenous contrast agents or chemotherapy drugs);
Exclusion criteria (Two)
9. Within 4 weeks before the first dose of study treatment or plan to receive live attenuated vaccine during the study period;
10. Have received major surgery (craniotomy, thoracotomy or laparotomy) within 4 weeks before the first dose of study treatment, or expect major surgery during the study treatment period (except for PICC and deep venous catheterization);
11. Before enrollment, there was toxicity caused by previous anti-tumor therapy that did not return to NCI CTCAE V5.0 0~1;
12. Patients with active uncontrolled coagulation disorders requiring therapeutic use of anticoagulant drugs (such as warfarin, low molecular weight heparin, etc.);
13. Known active or suspicious autoimmune disease or history of the disease within the past 2 years (Vitiligo, psoriasis, Hashimotos thyroiditis or Graves disease that does not require systemic treatment within the past 2 years Subjects with hypothyroidism who only require thyroid hormone replacement therapy and type I diabetes who only require insulin replacement therapy can be enrolled);
14. Known history of primary immunodeficiency;
15. Known history of active tuberculosis;
16. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
Exclusion criteria (Three)
17. Uncontrolled concurrent diseases include but are not limited to:
(1)HIV-infected persons (HIV antibody positive);
(2)Severe infections that are in the active phase or poorly clinically controlled;
(3)Symptomatic congestive heart failure (New York Heart Association Grade II~IV) or symptomatic or poorly controlled arrhythmia;
(4)Arterial hypertension (systolic blood pressure >=160 mmHg or diastolic blood pressure >=100 mmHg) that is still uncontrolled even with standard treatment;
(5)Any arterial thromboembolic events, including myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack occurred within 6 months before being selected for treatment;
(6)Esophageal or gastric varices that require immediate intervention (for example, banding or sclerotherapy), or according to the opinion of the investigator or consulting a gastroenterologist or hepatologist who believes that the bleeding risk is higher, and there is evidence of portal hypertension (including imaging Subjects with a history of splenomegaly on medical examination or a history of varicose bleeding must undergo endoscopic evaluation within 3 months before enrollment;
(7)Have a history of gastrointestinal perforation and/or fistula within 6 months before enrollment in the study.
(8)Any life-threatening bleeding events such as intracranial hemorrhage or grade 3 or 4 gastrointestinal/varices bleeding events requiring blood transfusion, endoscopic or surgical treatment occurred within 6 months before the enrollment in the study;
(9) A history of deep vein thrombosis, pulmonary embolism or any other serious thromboembolism within 6 months before enrollment (implantable venous port or catheter-induced thrombosis, or superficial vein thrombosis is not considered as "serious "Thrombus embolism);
(10) Uncontrolled metabolic disorders or secondary reactions of other non-malignant tumor organs or systemic diseases or cancers, which may lead to higher medical risks and/or uncertainty in survival evaluation;
(11) Hepatic encephalopathy, hepatorenal syndrome or Child-Pugh grade B or more severe liver cirrhosis;
(12) A history of bowel obstruction or the following diseases: inflammatory bowel disease or extensive bowel resection (partial colectomy or extensive small bowel resection, complicated by chronic diarrhea), Crohns disease, ulcerative colitis, or chronic diarrhea;
(13) Other acute or chronic diseases, mental illnesses, or abnormal laboratory test values ??that may cause the following results: increase the risk related to research participation or research drug administration, or interfere with the interpretation of research results, and will be tested according to the judgment of the researcher Those who are classified as not eligible to participate in this study;
(14) Acute or chronic active hepatitis B or C infection: HBsAg positive and hepatitis B virus (HBV) DNA>200 IU/ml or 1000 copies/ml; hepatitis C virus (HCV) antibody is positive and RNA is positive ;
Exclusion criteria (Four)
18. History of other primary malignant tumors, except:
(1) Malignant tumors that have been cured, no known active disease for >= 5 years before being selected for the study, and the risk of recurrence is extremely low;
(2) Non-melanoma skin cancer or malignant freckle-like nevus that has been adequately treated and has no evidence of disease recurrence;
(3) Carcinoma in situ with adequate treatment and no evidence of disease recurrence.
19. Female subjects who are pregnant or breastfeeding;
20. Other researchers think it is not suitable for inclusion in the group.

研究实施时间：

Study execute time：

从 From 2021-05-04 00:00:00至 To 2023-05-04 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2021-05-04 00:00:00 至 To 2023-05-04 00:00:00

干预措施：

Interventions：

组别：

组1

样本量：

 53

Group：

Group 1

Sample size：

干预措施：

Tislelizumab联合HMA和阿糖胞苷治疗在中高危骨髓增生异常综合征；入组患者接受至少2个疗程的治疗，评估有效性及安全性。

干预措施代码：

Intervention：

Tislelizumab combined with HMA and cytarabine in the treatment of medium to high-risk myelodysplastic syndromes; enrolled patients received at least two courses of treatment to evaluate the effectiveness and safety.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 湖北 

市(区县)：

 武汉 

Country：

China

Province：

Hubei

City：

Wuhan

单位(医院)：

 华中科技大学同济医学院附属协和医院 

单位级别：

 三级甲等 

Institution
hospital：

Union Hospital, Tongji Medical College of HUST

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

骨髓细胞学

指标类型：

主要指标

Outcome：

Bone marrow cytology

Type：

Primary 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 - 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）：

-

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

-

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）：

Calculated Results after
the Study Completed(upload file)：

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）：

-

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

-

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：

本研究将采用电子数据采集（ElectronicDataCapture,EDC）系统，研究数据将由研究者或授权的研究人员录入到eCRF中。研究中心启动或数据录入前，将对研究者和授权的研究人员进行适当培训，并对所使用的电脑等设备采取适当的安全措施。 eCRF的数据录入应于访视期间或之后尽快完成，并随时更新，以保证其能够反映参加研究的受试者的最新动态。为避免不同评估者的评估差异，建议同一受试者的基线及所有后续疗效和安全性评估均由同一人员完成。研究者须审核数据，以确保录入到eCRF中的所有数据的准确性和正确性。若研究过程中未进行某些评估，或者某些信息不可用、不适用、未知，研究者应将其记录在eCRF中。研究者应对核查后的数据进行电子签名。 临床监查员（ClinicalResearchAssociate,CRA）将审阅eCRF，并评估其完整性和一致性，CRA将对eCRF和原始文件进行对比，以确保关键数据的一致性。所有数据的录入、更正和修改都将由研究者或其指定人员负责。eCRF中的数据提交至数据服务器，对数据的任何更改均将记录于稽查轨迹中，即更改原因、操作者姓名、修改时间和日期都将被记录。将预先确定研究中心负责数据录入的工作人员的角色和权限。如有数据质疑，CRA或数据管理人员将在电子数据采集（Electronicdatacapture,EDC）系统中发出质疑，并由研究中心工作人员负责答疑。 EDC系统将记录质疑的稽查轨迹，包括研究者姓名、时间和日期。

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

An electronic data capture (EDC) system will be used for this study and study data will be entered into the eCRF by the investigator or authorized study personnel. Prior to site initiation or data entry, appropriate training will be provided to the investigators and authorized study personnel, and appropriate security measures will be taken for computers and other equipment used. Data entry into the eCRF should be completed during or as soon as possible after the visit and updated at any time to ensure that it reflects the latest status of subjects participating in the study. To avoid assessment differences by different assessors, it is recommended that the baseline and all subsequent efficacy and safety assessments for the same subject be completed by the same person. The investigator must review the data to ensure accuracy and correctness of all data entered in the eCRF. If some assessments are performed during the study, or some information is unavailable, not applicable, or unknown, the investigator should record it in the eCRF. The investigator should electronically sign the verified data. The clinical research associate (CRA) will review the eCRF and assess its completeness and consistency. The CRA will compare the eCRF with the original documents to ensure consistency of key data. All data entry, correction, and modification will be the responsibility of the investigator or designee. The data in the eCRF will be submitted to the data server, and any changes to the data will be recorded in the audit trail, i.e. the reason for the change, the name of the operator, the time and date of the change will all be recorded. The roles and authorities of the site staff responsible for data entry will be predetermined. In case of data query, CRA or data management personnel will issue a query in the electronic data capture (EDC) system and the site staff will be responsible for answering the query. The EDC system will document the audit trail of the query, including the investigator's name, time, and date.

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：

  2021-04-10 07:57:22