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：	ChiCTR2500102128
最近更新日期： Date of Last Refreshed on：	2025-05-09 08:54:15
注册时间： Date of Registration：	2025-05-09 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	恩那度司他治疗骨髓纤维化相关贫血有效性及安全性的前瞻性、随机对照、多中心、II/III期临床研究
Public title：	Efficacy and Safety of Ennatostat in the Treatment of Anemia Associated with Myelofibrosis: A Prospective, Randomized Controlled, Multicenter, Phase II/III Clinical Trial
注册题目简写：
English Acronym：
研究课题的正式科学名称：	恩那度司他治疗骨髓纤维化相关贫血有效性及安全性的前瞻性、随机对照、多中心、II/III期临床研究
Scientific title：	Efficacy and Safety of Ennatostat in the Treatment of Anemia Associated with Myelofibrosis: A Prospective, Randomized Controlled, Multicenter, Phase II/III Clinical Trial
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：	杨丽清	研究负责人：	吴勇
Applicant：	Liqing Yang	Study leader：	Yong Wu
申请注册联系人电话： Applicant telephone：	+86 156 8085 0730	研究负责人电话： Study leader's telephone：	+86 133 6591 0911
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：	18896750620@163.com	研究负责人电子邮件： Study leader's E-mail：	wuyong9195@126.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：	福建省福州市新权路29号福建医科大学附属协和医院	研究负责人通讯地址：	福建省福州市新权路29号福建医科大学附属协和医院
Applicant address：	Fujian Medical University Union Hospital, Fujian Medical University, No.29 Xinquan Road, Fuzhou, Fujian, China	Study leader's address：	Fujian Medical University Union Hospital, Fujian Medical University, No.29 Xinquan Road, Fuzhou, Fujian, China
申请注册联系人邮政编码： Applicant postcode：	350001	研究负责人邮政编码： Study leader's postcode：	350001
申请人所在单位：	福建医科大学附属协和医院
Applicant's institution：	Fujian Medical University Union Hospital
研究负责人所在单位：	福建医科大学附属协和医院
Affiliation of the Leader：	Fujian Medical University Union 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：	2025YF022-01	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：	福建医科大学附属协和医院伦理委员会
Name of the ethic committee：	ethic committee of Fujian Medical University Union Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2025-05-06 00:00:00
伦理委员会联系人：	赖晓玉
Contact Name of the ethic committee：	Xiao-yu Lai
伦理委员会联系地址：	福建省福州市新权路29号福建医科大学附属协和医院
Contact Address of the ethic committee：	Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 591 8621 8341	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：

福建医科大学附属协和医院

Primary sponsor：

Fujian Medical University Union Hospital

研究实施负责（组长）单位地址：

福建省福州市新权路29号福建医科大学附属协和医院

Primary sponsor's address：

Fujian Medical University Union Hospital, Fujian Medical University, No.29 Xinquan Road, Fuzhou, Fujian, 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)：	福建	市(区县)：	福州
Country：	China	Province：	Fujian	City：	Fuzhou
单位(医院)：	福建医科大学附属协和医院	具体地址：	福建省福州市新权路29号福建医科大学附属协和医院
Institution hospital：	Fujian Medical University Union Hospital	Address：	Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, China

经费或物资来源：

中央引导地方科技发展资金项目（编号：2023L3010）

Source(s) of funding：

Central Guiding Local Technology Development Funds Project‌ (Grant no. 2023L3010)

研究疾病：

骨髓增殖性肿瘤

Target disease：

myeloproliferative neoplasm

研究疾病代码：

H0808

Target disease code：

H0808

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

II期临床试验

Study phase：

2

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

一项单中心、前瞻性、随机对照临床研究。纳入2025.04至2027.04于福建医科大学附属协和医院就诊的骨髓纤维化相关贫血患者，随机（3：2）接受口服含或不含恩那度司他方案，均给予最佳支持治疗，整个疗程分为24个治疗周及4个随访观察周。参加本试验的受试者经过筛选期、治疗期、访视，试验过程中记录受试者的入选情况、治疗情况及随访情况，用于评价恩那度司他治疗骨髓纤维化相关贫血的有效性及安全性。

Objectives of Study：

A single-center, prospective, randomized controlled clinical study. Patients with myelofibrosis-associated anemia attending Fujian Medical University Union Hospital from 2025.04 to 2027.04 were enrolled and randomized (3:2) to receive an oral regimen with or without enanthostat, all of whom were given optimal supportive therapy, and the entire course of treatment was divided into 24 treatment weeks and 4 follow-up observation weeks. Subjects enrolled in this trial underwent a screening period, a treatment period, and a visit; enrollment, treatment, and follow-up were recorded during the trial and used to evaluate the efficacy and safety of ennatostat in the treatment of myelofibrosis-related anemia.

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

Subjects must meet all of the following criteria to be enrolled in this study:
1. age 18 to 90 years (including upper and lower limits), male or female;
2. a definitive diagnosis of primary myelofibrosis (PMF), post-positive erythrocytosis myelofibrosis (post-PV MF), or post-positive thrombocytosis myelofibrosis (post-ET MF) according to the 2022 WHO guidelines for the diagnosis of chromosome-negative MPN in Philadelphia, with screening/baseline bone marrow morphology and immunophenotyping of primitive cells <10%, and biopsies showing MF >=  grade 2;
3. symptomatic anemia: HB < 8.0 g/dL >=  2 times (>=  7 days apart), including transfusion-dependent subjects, i.e., transfusion load of >=  1 pRBC unit every 8 weeks;
4. not expected to undergo hematopoietic cell transplantation within 7 months of enrollment and have a life expectancy of at least 28 weeks;
5. an Eastern Cooperative Oncology Group (ECOG) physical status score of <= 3 at the time of enrollment
6. willingness to avoid pregnancy or childbirth based on the following criteria:
a. female subjects of non-fertile potential (i.e., surgically sterilized by hysterectomy and/or bilateral salpingo-oophorectomy or amenorrheic for >=  12 months and >=  50 years of age) are eligible to participate in the study;
b. Female subjects of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test prior to the first dose on Day 1, and must agree to use adequate contraception (contraceptive success rate of at least 99%) from Screening through Safety Follow-Up. Available methods with a contraceptive success rate of at least 99% should be communicated to the subject and his/her understanding should be confirmed;
c. Male subjects of childbearing potential must agree to use appropriate contraception (with a contraceptive success rate of at least 99%) from Screening until 93 days after the last dose of study drug and must not donate sperm during this time. Available methods of contraception with at least a 99% success rate should be communicated to the subject and his/her understanding should be verified;
7. be able to understand the procedures and methodology of this clinical trial and, with fully informed consent, the subject voluntarily participates and voluntarily signs an informed consent form in writing by himself/herself or legal representative;
8. the subject is willing and able to comply with the study visit schedule and other protocol requirements.

排除标准：

符合下列任一标准的受试者均不能入组： 1. 其他原因导致的贫血（如缺铁性贫血、B12和叶酸缺乏症、溶血性贫血、感染或出血等）。 2. 铁储存不足（铁蛋白<50 ng/mL）。 3. 基础内源性血清EPO＞500 mIU/mL。 4. 筛选/入组之前8周内接受过ESAs治疗。 5. 在开始治疗前，重大手术的副作用/或并发症尚未充分恢复。 6. 骨髓储备不足的近期病史（示例包括但不仅限于下述）： a. 筛选前或在筛选实验室评估时 4 周内血小板计数＜50×109/L 或筛选前 8 周内输注血小板。 b. 筛选前或在筛选实验室评估时 4 周内中性粒细胞绝对计数＜0.5×109/L或筛选前8 周内接受过粒细胞集落刺激因子（G-CSF）治疗。 7. 造血细胞移植术后。 8. 目前处于哺乳期或妊娠期。 9. 在过去2年内患有活动性侵袭性恶性肿瘤，已治疗的皮肤基底或鳞状细胞癌、完全切除的宫颈上皮内癌以及甲状腺乳头状癌和滤泡状癌除外。患有惰性恶性肿瘤（如接受放疗或手术治疗的前列腺癌）的受试者治愈后可入组。 10. 受试者在入组前8周内参与任何其他临床方案或研究试验，包括实验治疗和/或治疗装置的给药。 11. 筛选访视时肝功能不全，证据如下： a. 总胆红素>2.0×正常值上限（ULN）。注：如果总胆红素>2.0×ULN 且直接胆红素<2.0×ULN，则受试者可以入组。 b. 丙氨酸氨基转移酶（ALT）或天冬氨酸氨基转移酶（AST）＞3×ULN或肝功能损害CTCAE等级≥3的患者。 12. 入组前6个月内出现脑卒中、心肌梗死、深静脉血栓形成、肺动脉栓塞等血栓栓塞事件史。 13. 高血压病史，或筛选期间测得舒张压≥90mmHg或收缩压≥140mmHg。以及其他研究者认为可能危及受试者安全或方案依从性的不受控制的重度或不稳定心脏疾病。 14. 已知对恩那度司他、安慰剂的辅料有超敏反应或重度反应。 15. 需要治疗的活动性细菌、真菌、寄生虫或病毒感染。需要治疗的急性感染受试者应延迟筛选/入组，直至治疗过程完成且认为事件消退。允许使用预防性抗生素或抗病毒药。 16. 需要治疗的活动性慢性乙型或丙型肝炎（HBV/HCV）感染，及已知HIV等血液传染病。 17. 可能干扰研究要求依从性的活动性酒精或药物成瘾。 18. 存在研究者判断会干扰研究全程参与（包括研究药物给药和参加必须的研究访视、对受试者有重大风险或对研究数据解读造成干扰的情况。 19. 在研究药物首次给药前 30 天内接受过任何活疫苗。

Exclusion criteria：

Subjects meeting any of the following criteria are not eligible for enrollment: 1. other causes of anemia (e.g., iron deficiency anemia, B12 and folate deficiencies, hemolytic anemia, infections, or bleeding) 2. inadequate iron stores (ferritin <50 ng/mL). 3. basal endogenous serum EPO >500 mIU/mL. 4. treatment with ESAs within 8 weeks prior to screening/enrollment. 5. has not fully recovered from the side effects/ or complications of major surgery prior to initiation of therapy. 6. recent history of inadequate bone marrow reserve (examples include, but are not limited to, the following): a. Platelet count <50 x 10^9/L within 4 weeks prior to screening or at the time of screening laboratory evaluation or platelet transfusion within 8 weeks prior to screening. b. Absolute neutrophil count <0.5 x 10^9/L within 4 weeks prior to screening or at the time of evaluation at the screening laboratory or treatment with granulocyte colony-stimulating factor (G-CSF) within 8 weeks prior to screening. 7. After hematopoietic cell transplantation. 8. currently lactating or pregnant. 9. have an active aggressive malignancy within the past 2 years, with the exception of treated basal or squamous cell carcinoma of the skin, completely resected intraepithelial carcinoma of the cervix, and papillary and follicular carcinoma of the thyroid. Subjects with inert malignancies (e.g., prostate cancer treated with radiotherapy or surgery) may be enrolled after cure. 10. subject's participation in any other clinical protocol or research trial, including administration of experimental treatments and/or therapeutic devices, within 8 weeks prior to enrollment. 11. hepatic insufficiency at the screening visit as evidenced by the following: a. total bilirubin > 2.0 x upper limit of normal (ULN). Note: Subjects may be enrolled if total bilirubin > 2.0 x ULN and direct bilirubin < 2.0 x ULN. b. Patients with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x ULN or CTCAE class >= 3 for hepatic impairment. 12. history of thromboembolic events such as stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism within 6 months prior to enrollment. 13. history of hypertension, or diastolic blood pressure >= 90 mmHg or systolic blood pressure >= 140 mmHg measured during Screening. and other uncontrolled severe or unstable cardiac disease that, in the opinion of the investigator, may jeopardize subject safety or compliance with the regimen. 14. known hypersensitivity or severe reaction to enalastat, placebo excipients. 15. active bacterial, fungal, parasitic or viral infection requiring treatment. Subjects with acute infections requiring treatment should have screening/enrollment delayed until the course of treatment is complete and the event is considered to have subsided. Prophylactic antibiotics or antivirals are permitted. 16. active chronic hepatitis B or C (HBV/HCV) infection requiring treatment, and known blood-borne infections such as HIV. 17. active alcohol or drug addiction that may interfere with compliance with study requirements. 18. the presence of conditions that, in the judgment of the Investigator, would interfere with full participation in the study (including administration of study drug and participation in required study visits, pose a significant risk to subjects, or interfere with the interpretation of study data. 19. has received any live vaccine within 30 days prior to the first dose of study drug.

研究实施时间：

Study execute time：

从 From 2025-05-09 00:00:00至 To 2027-04-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-05-09 00:00:00 至 To 2027-04-30 00:00:00

干预措施：

Interventions：

组别：	对照组	样本量：	20
Group：	Control group	Sample size：	20
干预措施：	芦可替尼+强的松+达那唑联合沙利度胺	干预措施代码：	0
Intervention：	Rucotinib + prednisone + danazol combined with thalidomide	Intervention code：	0

组别：	试验组	样本量：	30
Group：	Experimental group	Sample size：	30
干预措施：	芦可替尼+强的松+达那唑联合恩那度司他	干预措施代码：	1
Intervention：	Rucotinib + prednisone + danazol combined with ennatostat	Intervention code：	1

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	福建	市(区县)：	福州
Country：	China	Province：	Fujian	City：	Fuzhou
单位(医院)：	福建医科大学附属协和医院	单位级别：	三甲
Institution hospital：	Fujian Medical University Union Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	红系应答比例	指标类型：	主要指标
Outcome：	Red lineage response rate	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	脱离输血依赖的受试者比例	指标类型：	主要指标
Outcome：	Proportion of subjects removed from transfusion dependence	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	红系应答反应时间	指标类型：	次要指标
Outcome：	Time to red lineage response	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	红系应答反应持续时间	指标类型：	次要指标
Outcome：	Duration of red lineage response	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	次红系应答反应比例	指标类型：	次要指标
Outcome：	Second red lineage response rate	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	红细胞输注单位改变	指标类型：	次要指标
Outcome：	Changes in red blood cell transfusion unites	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	红细胞输血依赖的改变频率	指标类型：	次要指标
Outcome：	Frequency of alterations in red blood cell transfusion dependence	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	脱离输血依赖的持续反应时间	指标类型：	次要指标
Outcome：	Duration of sustained response time to withdrawal from transfusion dependence	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	血红蛋白变化	指标类型：	次要指标
Outcome：	Changes in hemoglobin	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：	骨髓	组织：
Sample Name：	bone marrow	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

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	90	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）：

受试者在入组后立即按照3:2的比例分配至恩那度司他组和安慰剂组。采用区组随机化+分层控制的方法。区组大小=4，由统计师编程产生随机分组盲底并导入IWRS系统。各中心按照受试者招募顺序竞争入组，不同中心可共享同一区组内随机编码。由各中心研究者向IWRS系统输入受试者的相关信息（包括但不限于：随机类型、中心编号、受试者姓名缩写、受试者筛选号、年龄、性别、HB水平等），并提交申请。IWRS系统为受试者分组时，依循随机盲底并加以分层控制。分层包括：1. 年龄：18-60岁为低年龄，大于60岁为高年龄。2. HB水平：中度贫血（6.0-8.0 g/dL）、重度贫血（<6.0 g/dL）。

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

Subjects were assigned to the ennatostat and placebo groups in a 3:2 ratio immediately after enrollment. A block group randomization + stratified control method was used. The block group size = 4 was programmed by a statistician to generate blinded bottoms for the randomized groups and imported into the IWRS system. Centers competed for enrollment in order of subject recruitment, and different centers could share randomization codes within the same block group. The investigator at each center enters the subject's information (including but not limited to: randomization type, center number, subject's initials, subject screening number, age, gender, HB level, etc.) into the IWRS system and submits an application.The IWRS system follows the randomized blinded base when grouping subjects and controls for stratification. Stratification included: 1. age: 18-60 years old for low age and >60 years old for high age; 2. HB level: moderate anemia (6.0-8.0 g/dL), severe anemia (<6.0 g/dL).z

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：	双盲
Blinding：	Double blinded

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）：	不共享
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	NA
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：	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：	2025-05-09 08:54:10