ChiCTR2100052858 版本V1.0 版本创建时间2021/11/6 1:26:39 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:

ChiCTR2100052858 

最近更新时间:

Date of Last Refreshed on:

2021/11/6 1:26:28 

注册号状态:

预注册  

Registration Status:

Prospective registration  

填写语言:

中文和英文  

Language:

Chinese And English  

注册题目:

自体CRISPR-Cas9编辑的CD34阳性细胞(RM-001)治疗输血依赖型β-地中海贫血症的安全性和有效性探索 

Public title:

Safety and Efficacy Evaluation of RM-001 for the treatment of transfusions dependent β-Thalassaemia Major 

注册题目简写:

 

Public title acronym:

 

研究课题的正式科学名称:

自体CRISPR-Cas9编辑的CD34阳性细胞(RM-001)治疗输血依赖型β-地中海贫血症的安全性和有效性探索临床研究方案 

Scientific title:

The Safety and Efficacy Evaluation of RM-001 for the treatment of transfusions dependent β-Thalassaemia Major in clinical trials 

研究课题的正式科学名称简写:

 

Scientific title acronym:

 

研究课题代号(代码):

Study subject ID:

 

在其它机构的注册号:

Secondary ID:

 

申请注册联系人:

尹晓林 

研究负责人:

张新华 

Applicant:

Xiaolin Yin 

Study leader:

Xinhua Zhang 

申请注册联系人电话:

Applicant telephone:

+86 13321717899 

研究负责人电话:

Study leader's telephone:

+86 13321717386 

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:

yin-xl@163.com 

研究负责人电子邮件:

Study leader's E-mail:

zxh303xy@163.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:

广西南宁市青秀区植物路52号 

研究负责人通讯地址:

广西南宁市青秀区植物路52号 

Applicant address:

52 Zhiwu Road, Qingxiu District, Nanning City, Guangxi Province, China 

Study leader's address:

52 Zhiwu Road, Qingxiu District, Nanning City, Guangxi 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:

解放军联勤保障部队第九二三医院 

Applicant's institution:

923rd Hospital of The People's Liberation Army 

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:

303LL-KY-2021-001-01 

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:

中国人民解放军联勤保障部队第九二三医院伦理委员会 

Name of the ethic committee:

Ethics Committee of the 923rd Hospital of the Chinese People's Liberation Army Joint Logistic Support Force 

伦理委员会批准日期:

Date of approved by ethic committee:

2021-08-25 

国家FDA批准文号:

Approved No. of SFDA:

国家FDA批准附件:

Approved file of SFDA:

国家FDA批准日期:

Date of approved by SFDA:

研究实施负责(组长)单位:

解放军联勤保障部队第九二三医院 

Primary sponsor:

923rd Hospital of The People's Liberation Army 

研究实施负责(组长)单位地址:

广西南宁市青秀区植物路52号 

Primary sponsor's address:

52 Zhiwu Road, Qingxiu District, Nanning City, Guangxi 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):

广西

市(区县):

南宁

Country:

China

Province:

Guangxi

City:

Nanning

单位(医院):

解放军联勤保障部队第九二三医院

具体地址:

青秀区植物路52号

Institution
hospital:

The 923rd Hospital of the People's Liberation Army

Address:

52 Zhiwu Road, Qingxiu District

国家:

中国

省(直辖市):

广东

市(区县):

广州

Country:

China

Province:

Guangdong

City:

Guangzhou

单位(医院):

南方医科大学

具体地址:

白云区沙太南路1023号

Institution
hospital:

Southern Medical University

Address:

1023 Shatai Road South, Baiyun District

经费或物资来源:

自筹经费 

Source(s) of funding:

Self-raised funds 

研究疾病:

β-地中海贫血症 

Target disease:

β-thalassemia 

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:

探索性研究/预试验 

Study phase:

研究目的:

初步探索CRISPR-Cas9编辑的自体CD34阳性细胞(RM-001)用于治疗输血依赖型β地中海贫血症的安全性及有效性。 

Objectives of Study:

To explore the safety and efficacy of CRISPR-Cas9-edited autologous CD34 positive cells (RM-001) for the treatment of transfusions dependent β-Thalassaemia Major. 

研究设计:

单臂 

Study design:

Single arm 

纳入标准:

符合以下所有条件者才能入选本试验: 1.确诊患者输血依赖型β-地中海贫血; 2.无HLA配型10/10全相合的同胞或无关供者可行异基因造血干细胞移植治疗; 3.患者自愿签署知情同意书(成人或法定代理人)并能完成研究程序和随访检查与治疗; 4.年龄6周岁~35周岁,性别不限; 5.每年输血>100 ml/kg; 6.输血前的报告基线Hb浓度≤7/dL; 7.临床稳定,适合接受HSCT; 8.具有合适的器官功能储备;; 9.具备单个核细胞采集的血管条件; 10.育龄期妇女在RM-001输注前7天内的血/尿妊娠试验为阴性,任何有生育能力的男性和女性患者必须同意在整个研究过程中以及研究治疗给药后至少一年内使用有效的避孕方法。根据研究者的判断,患者有生育能力是指:他/她生物学上有能力有孩子以及有正常的性生活。没有生育能力的女性患者(即,满足至少1条以下标准): (1)已行子宫切除术或双侧卵巢切除术,或 (2)经医学确认卵巢衰竭,或 (3)医学确认为绝经后(至少连续12个月停经)。 

Inclusion criteria

The subjects must meet all of the following conditions: 1.Clinically diagnosed as TDT, the genotypes mainly include: β0β0, β+β0, βEβ0 and β+/β+; 2.Without a HLA 10/10 matched sibling or unrelated stem cell donor to process a allogeneic transplantation; 3.Be able to provide written consent (adults, or legal guardians, as applicable) or assent (adolescents). 4.Subjects between 6 and 35 years of age, inclusive, at the time of consent or assent (as applicable); 5.A history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year during the prior 2 years. 6.Documented baseline, or pretransfusion, Hb level ≤7 g/dL. 7.Has a proper reserve of viscera function, including heart function, lung function, liver function and kidney function. 8.Clinically stable, have a Karnofsky performance status of ≥ 60, and eligible to undergo HSCT. 9.Has a proper vascular conditions for collecting mononuclear cells. 10.Female of reproductive age who has a negative blood/urine pregnancy test within 7 days prior to the RM-001 infusion, male/female must agree to use an effective contraceptive method throughout the study and for at least half a year after the study therapy. 

排除标准:

符合以下任何一项者将被排除: 1.如下病毒检测呈阳性患者:HIV-1/2、HTLV、HCMV、EB、COVID-19。乙肝表面抗原(HBsAg)阳性、乙肝e抗原(HBeAg)阳性、乙肝e抗体(HBeAb)阳性 、乙肝核心抗体(HBcAb)阳性、丙肝抗体(HCV-Ab)阳性、抗梅毒螺旋体抗体(TP-Ab)阳性,符合其中一项者。 2.筛选时有未控制的活动性感染(例如败血症、菌血症、真菌血症、病毒血症等); 3.非脾脏功能亢进导致的白细胞计数<3x10^9/L,和/或血小板数<100x10^9/L; 4.凝血功能异常; 5.晚期肝脏病变。表现为基线丙氨酸转氨酶或胆红素值超过3倍正常值,或者表现为肝脏活检提示肝硬化、往肝纤维化发展或肝炎。 6.曾接受过异基因造血干细胞移植(allo-HSCT)的患者。 7.心功能异常。 8.在入排筛选期的30天内,参与其他临床研究。 9.已知对试验中所用制剂成分有超敏反应史者。 10.筛选前6周内接种过活疫苗。 11.现患或有中枢神经系统疾病史的患者,如癫痫发作、脑血管缺血/出血、瘫痪、失语、中风、严重脑损伤、痴呆、帕金森病、小脑疾病、脑器质性综合征、精神疾病或任何伴累及中枢神经系统的自身免疫性疾病。 12.曾患有或正患有恶性肿瘤、髓系异常增生或免疫缺陷疾病。既往有恶性肿瘤史,疾病已治愈≥5年的患者可以入选。 13.直系亲属具有或怀疑具有遗传性癌症(例如,遗传性乳腺癌、遗传性非息肉结直肠癌)。 14.已知患者患有系统性血管炎(例如Wegener肉芽肿、结节性多动脉炎)、 系统性红斑狼疮、合并活动性或未经控制的自身免疫性疾病(例如Crohns病、类风湿关节炎、自身免疫性溶血性贫血等)、原发性或者继发性免疫缺陷(例如HIV感染或者严重感染性疾病等)。 15.为怀孕、哺乳的女性;在移植成功后1年内,不愿意进行避孕的男性或女性。 16.研究者认为不适合参加本临床试验的其他情况。 

Exclusion criteria:

Subjects cannot be enrolled into this study if they meet any of the following conditions: 1.Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), hepatitis B virus (HBV), or hepatitis C virus (HCV). Where clinically and/or regionally indicated, one or more of the following tests may be performed, in which case positive results would exclude the subject from participating: human T-lymphotrophic virus-1 (HTLV-1) or HTLV-2, Syphilis (RPR),Cytomegalovirus(CMV), or COVID-19. 2.Active bacterial, viral, fungal, or parasitic infection. 3.A white blood cell (WBC) count < 3 × 10^9/L, and / or platelet count < 100 × 10^9/L if not due to Hypersplenism. 4.Uncorrected Coagulation disorders. 5.Advanced liver disease, defined as:1).Baseline alanine transaminase or direct bilirubin value >3 × the upper limit of normal (ULN), or 2).Liver biopsy demonstrating cirrhosis, any evidence of bridging fibrosis, or active hepatitis. 6.Prior allo-HSCT. 7.Cardiac dysfunction. 8.Participation in another clinical study with an investigational drug within 30 days of Screening. 9.Those who are known to be allergic to hematopoietic stem cell mobilizer (plerixafor/G-CSF), Busulfan injection, DMSO or any other reagents using during the process of manufacturing RM-001. 10.Live vaccine was inoculated within 6 weeks before the screening period. 11.Patients who currently have or have a history of central nervous system disorders, such as epileptic seizures, cerebrovascular ischemia/hemorrhage, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, mental illness, or any autoimmune disease associated with central nervous system involvement. 12.Has or is suffering from a malignant tumor, myeloid dysplasia or immune deficiency disease. Patients with a prior history of malignancy and a disease that has been cured for at least 5 years were eligible for inclusion. 13.A cardiac T2* < 10 ms by magnetic resonance imaging (MRI).A liver T2* < 1.4 ms or >14mg/g by magnetic resonance imaging (MRI). 14. Serum Ferritin was over 5000ng/ml. Or any other evidence of severe iron overload that, in the investigators opinion, warrants exclusion. 15. Failure to obtain appropriate informed consent / assent. 16. Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects. Females of child-bearing potential are required to use effective contraception from Screening through at least 6 months after drug product infusion. Male subjects are required to use effective contraception. 

研究实施时间:

Study execute time:

From2021-11-08To 2024-08-31 

干预措施:

Interventions:

组别:

治疗组

样本量:

10

Group:

Therapy group

Sample size:

干预措施:

RM-001细胞输注

干预措施代码:

Intervention:

RM-001 cells infusion

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

广西 

市(区县):

南宁 

Country:

China 

Province:

Guangxi 

City:

Nanning 

单位(医院):

解放军联勤保障部队第九二三医院 

单位级别:

三级甲等 

Institution
hospital:

The 923rd Hospital of the People's Liberation Army  

Level of the institution:

Tertiary 

测量指标:

Outcomes:

指标中文名:

血红蛋白

指标类型:

主要指标 

Outcome:

Hemoglobin

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

等位基因

指标类型:

次要指标 

Outcome:

Allele

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

输血次数

指标类型:

次要指标 

Outcome:

Number of blood transfusion

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

疾病相关事件发生次数

指标类型:

次要指标 

Outcome:

Number of disease-related events

Type:

Secondary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

胎儿血红蛋白红细胞

指标类型:

主要指标 

Outcome:

Hemoglobin F

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

中性粒细胞数量

指标类型:

附加指标 

Outcome:

Absolute neutrophil count

Type:

Additional indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

血小板

指标类型:

附加指标 

Outcome:

Platelet

Type:

Additional 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:

外周血

Sample Name:

Blood

Tissue:

Peripheral blood

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:

骨髓

组织:

骨髓

Sample Name:

Bone marrow

Tissue:

Bone marrow

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:

造血干细胞

组织:

外周血

Sample Name:

Stem cells

Tissue:

Peripheral blood

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:

正在进行

Recruiting

年龄范围:

Participant age:

最小 Min age 6 years
最大 Max age 35 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):

本研究采用单臂、不设盲、单中心的设计,不进行随机分组。

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

This is a single-arm, non-blinding, single-center design clinical study without random grouping.

UTN(全球唯一识别码):

盲法:

Blinding:

试验完成后的统计结果:

Calculated Results ater
the Study Completed:

研究负责(组长)单位:

Organizer institution (leader institution):

资料收集汇总单位:

0

Data collection Institution:

资料管理单位:

项目组根据研究进程择期选择具体方式公开原始数据

Data management Institution:

According to the progress of the research, raw research data should be made freely available to all researchers in specific ways

资料分析单位:

数据采集由两人共同完成,记录为病例记录表

Data analysis Institution:

The data was collected by two people and recorded as a case record

注册人:

Name on Registration:

 2021-11-06