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：	ChiCTR2300075013
最近更新日期： Date of Last Refreshed on：	2023-08-23 09:05:20
注册时间： Date of Registration：	2023-08-23 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	一项糖皮质激素联合泰它西普治疗IgG4相关性疾病的随机、双盲、单中心、安慰剂对照研究
Public title：	A randomized, double-blind, single-center, placebo-controlled study of glucocorticoids in combination with titacercept in the treatment of IgG4-RD
注册题目简写：
English Acronym：
研究课题的正式科学名称：	一项糖皮质激素联合泰它西普治疗IgG4相关性疾病的随机、双盲、单中心、安慰剂对照研究
Scientific title：	A randomized, double-blind, single-center, placebo-controlled study of glucocorticoids in combination with titacercept in the treatment of IgG4-RD
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：	胡紫薇	研究负责人：	董凌莉
Applicant：	Hu Ziwei	Study leader：	Dong Lingli
申请注册联系人电话： Applicant telephone：	+86 178 6642 2669	研究负责人电话： Study leader's telephone：	+86 178 6642 2669
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：	tongji_hzw@163.com	研究负责人电子邮件： Study leader's E-mail：	tongji_hzw@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：	湖北省武汉市硚口区解放大道1095号	研究负责人通讯地址：	湖北省武汉市硚口区解放大道1095号
Applicant address：	1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei	Study leader's address：	1095 Jiefang Avenue, Qiaokou 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同济医院
Applicant's institution：	Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
研究负责人所在单位：	华中科技大学同济医学院附属同济医院
Affiliation of the Leader：	Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology

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：	TJ-IRB20230756	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同济医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
伦理委员会批准日期： Date of approved by ethic committee：	2023-07-04 00:00:00
伦理委员会联系人：	杜艾桦
Contact Name of the ethic committee：	Du Aihua
伦理委员会联系地址：	湖北省武汉市硚口区解放大道1095号
Contact Address of the ethic committee：	1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 178 6642 2669	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：

华中科技大学同济医学院附属同济医院

Primary sponsor：

Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology

研究实施负责（组长）单位地址：

湖北省武汉市硚口区解放大道1095号

Primary sponsor's address：

1095 Jiefang Avenue, Qiaokou 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)：
Country：	China	Province：	Hubei	City：
单位(医院)：	华中科技大学同济医学院附属同济医院	具体地址：	湖北省武汉市硚口区解放大道1095号
Institution hospital：	Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology	Address：	1095 Jiefang Avenue, Qiaokou District, Wuhan, Hubei

经费或物资来源：

同济医院临床研究领航项目

Source(s) of funding：

Tongji Hospital Clinical Research Flagship Program

研究疾病：

IgG4相关性疾病

Target disease：

IgG4-RD

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：

0

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

通过前瞻性单臂研究探索激素联合泰它西普降低IgG4-RD 患者疾病复发风险的疗效，为泰它西普在IgG4相关性疾病中应用的有效性和安全性提供科学依据。

Objectives of Study：

A prospective single-arm study to explore the efficacy of the hormone combined with Taitacept in reducing the risk of disease recurrence in patients with IgG4-RD, and to provide a scientific basis for the efficacy and safety of Telitacicept in the treatment of IgG4-related diseases.

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

1. Patients should be at least 18 years old at the time of enrollment;
2. Obtain written informed consent from the subject and any authorizations required by the institution (e.g., data privacy) prior to conducting any procedures related to the study protocol, including screening assessments.
3. Clinical diagnosis was IgG4-RD.
4. According to the Qualification Committee, it meets the 2019 ACR/EULAR classification standard. 
5. Was experiencing (or had recently experienced) a recurrence of IgG4-RD that required the initiation or continuation of GC therapy at the time of informed consent.
6. At any time during the course of IgG4-RD, IgG4-RD involves at least two organs/sites, supported by documentary evidence. One organ must meet the requirements of the ACR/EULAR classification criteria (Inclusion Criterion 4); The second organ is defined by the researcher.
7. Willing and able to follow the study protocol, complete the study evaluation and complete the study period.
8. Unsterilized male subjects who have active sex with a potentially fertile female partner must use a condom containing spermicide (if spermicide is available) from day 1 to the end of the study and must agree to continue using such contraception for at least 6 months after the last dose.
Women with reproductive potential who are sexually active must use a highly effective contraceptive method from the time they sign an informed consent and must agree to continue using such contraceptive method until the end of the study follow-up period and until at least 180 days after the last dosing; Discontinuation of contraception after this time should be discussed with the responsible physician. Periodic abstinence, safe period contraception and external ejaculation are not acceptable methods of contraception. Female partners of male study participants (with reproductive potential) will be advised that they should use a highly effective method of contraception in addition to the barrier method.
Women with reproductive potential were defined as those who had not been surgically sterilized (surgical sterilization included bilateral tubal ligation, bilateral oophotomies, or hysterectomies) or were non-postmenopausal (defined as 12 months of menopause without other medical reasons, and clinical laboratory tests determined that FSH was in the postmenopausal range).

排除标准：

1. 存在严重的心血管、呼吸、内分泌、胃肠道、血液、神经系统、精神、或全身性疾病，或研究者认为可能使患者处于无法接受的并发症风险、干扰IP 评价或对患者安全性或研究结果的解释造成混杂的任何其他状况。 2. 有实体器官或细胞移植史。 3. 已知存在免疫缺陷疾病。 4. 存在活动性恶性肿瘤或在最近十年有活动性恶性肿瘤史，但以下情况除外： − 筛选前已行治愈性治疗超过12 个月的子宫颈原位癌， −经过治愈性治疗的皮肤基底细胞或鳞状细胞癌，或 − 筛选前已采用根治性前列腺切除术或治愈性放射疗法治疗超过3 年的前列腺癌，且无已知复发，当前也未接受治疗。 5. 在筛选前的6 个月内曾接受任何B 细胞耗竭生物疗法（例如，利妥昔单抗、ocrelizumab 、obinutuzumab 、ofatumumab、inebilizumab）。 6. 在筛选前6 个月内曾接受非消耗性B 细胞靶向治疗（例如belimumab）、abatacept 或其他生物免疫调节剂的受试者。 7. 在筛选前4 周内曾接受非生物DMARD 或除GC 以外的免疫抑制剂（例如硫唑嘌呤、霉酚酸酯、甲氨蝶呤等）。 8. 在筛选前12 周内或药物的5 个半衰期内（以较长者为准）曾接受任何试验性药物。 9. 据研究者认为，直到随机分组后8 周，受试者仍无法减量并停用GC 治疗（因治疗肾上腺功能不全或逐渐减量不耐受而服用泼尼松或等效药物≤2.5 mg/天的除外）。 10. 筛选前2 周内曾接受活疫苗或活的治疗性传染病原体。 11. 妊娠、哺乳或计划在末次IP 给药后6 个月内妊娠。 12. 乙肝或HIV 感染检测结果为阳性，或先前曾接受过相应治疗。乙肝检测结果阳性是指检测到（1）乙肝表面抗原（HBsAg）；或（2）乙肝核心抗体（抗HBc）。 13. 未治愈的丙肝感染史或丙肝病毒（HCV）抗体检测结果呈阳性，除非患者在抗病毒治疗后被认为已治愈，并且在研究中心或中心实验室完成治疗至少24 周后HCV 病毒载量低于检测限。 14. 存在活动性结核病（TB）的证据或基于以下证据患TB的风险较高： −有活动性TB 史或未治愈/未完全治愈的潜伏性TB 史。有活动性或潜伏性TB 病史但有证据表明已按当地指南完成治疗的患者可以入组。 −近期（筛选前12 周内）曾与活动性TB 患者发生密切接触（密切接触的定义为接触时间≥4 小时/周或生活在同一个家庭中，或生活在一名活动性TB 患者经常拜访的房屋中）。 −根据病史或体格检查发现存在可能代表活动性TB 的体征或症状。 −筛选时的干扰素-γ释放试验结果呈阳性、不确定或无效，除非先前曾接受过TB 治疗。测试结果不确定的患者可以重复测试一次，但是如果重复测试结果仍为不确定，则将患者排除。 − 胸部X 光片、胸部计算机断层扫描（CT）或MRI 扫描提示疑似TB 诊断或建议应进行TB 检查；所有患者必须在授予同意前6 个月内或筛查期间进行肺影像学检查，并获得可接受的结果。 15. 在筛选前的12 个月内曾有1 次以上带状疱疹（任何分级）和/或任何其他确定或可能的机会性感染的病史。 16. 已知对泰它西普制剂的任何成分有过敏史或反应史，或对任何人丙种球蛋白疗法有过敏史。 17. 对研究方案规定的治疗过敏或不耐受，包括用于预防输液反应的药物（退热药如对扑热息痛/对乙酰氨基酚或等效药物、苯海拉明或等效药物、以及甲基强的松龙或等效药物）。 18. 按照肾脏病饮食改良研究（MDRD）公式（NIDDK）计算的估计肾小球滤过率<30mL/min/1.73m²。 19. 筛选时进行的血液检查符合以下任何一项标准： − 血红蛋白< 7.5 g/dL − 中性粒细胞< 1200/mm3 − 血小板< 110 × 109/L − 嗜酸性粒细胞计数> 3000/mm3 − 凝血酶原时间＞1.2 x 正常值上限（ULN）；但是，不排除因房颤接受抗凝治疗且天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）≤2 x ULN 的受试者− 总免疫球蛋白＜600mg/dL − 筛选时CD19+B 细胞＜40 个细胞/μL；该排除值可重复。 20. 受试者在无肝胆IgG4-RD 活动的情况下存在以下异常肝功能检查结果： − 天冬氨酸转氨酶（AST）> 2 × ULN − 丙氨酸转氨酶（ALT）> 2 × ULN − 总胆红素（TBL） > 2 × ULN 筛选肝功能检查可在随机分组前重复进行，以允许因肝胆IgG4-RD 活动导致的异常值对GC 治疗产生反应。 21. 根据患者记录，已知靶向蛋白酶3 或髓过氧化物酶的抗中性粒细胞胞浆抗体（ANCA）阳性。 22. 有酗酒或吸毒史，据研究者认为可能会影响患者的安全性或访视依从性，或干扰安全性或其他研究评估。 23. 在随机分组时存在具有临床意义的活动性感染（如果在筛选时间窗内，可以推迟IP 给药直至康复，否则受试者可以进行重新筛选）。 24. 正在参与需要使用任何药物干预的任何临床试验。

Exclusion criteria：

1.The presence of serious cardiovascular, respiratory, endocrine, gastrointestinal, hematological, neurological, psychiatric, or systemic disease, or any other condition that the investigator believes may place the patient at an unacceptable risk of complications, interfere with the evaluation of IP, or confounding the interpretation of patient safety or study results. 2. A history of solid organ or cell transplantation. 3. Known immunodeficiency diseases. 4. Presence of active malignant tumor or history of active malignant tumor in the last 10 years, except in the following cases: - Cancer in situ of the cervix that has undergone curative treatment for more than 12 months prior to screening, − Basal cell or squamous cell carcinoma of the skin after curative treatment, or − Prostate cancer that has been treated with radical prostatectomy or curative radiation for more than 3 years prior to screening, has no known recurrence, and is not currently receiving treatment. 5. Received any B-cell depletion biologic therapy (e.g., rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab) in the 6 months prior to screening. 6. Subjects who have received non-expendable B-cell targeted therapy (e.g., belimumab), abatacept, or other biological immunomodulator in the 6 months prior to screening. 7. Received abiotic DMARD or immunosuppressants other than GC (e.g. Azathioprine, mycophenolate, methotrexate, etc.) in the 4 weeks prior to screening. 8. Received any investigational drug within 12 weeks prior to screening or within 5 half-lives of the drug. 9. According to the investigators, participants were unable to reduce and discontinue GC therapy until 8 weeks after randomization (except those taking prednisone or its equivalent ≤2.5 mg/ day for adrenal insufficiency or intolerance to tapering). 10. Received live vaccine or live therapeutic sexually transmitted pathogens within 2 weeks prior to screening. 11. Pregnancy, breastfeeding, or planning to become pregnant within 6 months after the last IP administration. 12. Have tested positive for hepatitis B or HIV infection, or have previously been treated accordingly. A positive hepatitis B test result means the detection of (1) Hepatitis B surface antigen (HBsAg); Or (2) Hepatitis B core antibodies (anti-HBC). 13. A history of uncured hepatitis C infection or a positive test result for antibodies to hepatitis C virus (HCV), unless the patient is considered cured after antiviral therapy and the HCV viral load is below the detection limit at least 24 weeks after completing treatment at a research center or central laboratory. 14. There is evidence of active tuberculosis (TB) or a higher risk of TB. 15. A history of more than 1 episode of shingles (of any grade) and/or any other established or probable opportunistic infection in the 12 months prior to screening. 16. A known history of allergy or reaction to any component of a formulation of titacept or to any gammaglobulin therapy by any person. 17. Allergy or intolerance to the treatment prescribed in the study protocol, including medications used to prevent infusion reactions (antipyretics such as paracetamol/acetaminophen or equivalent, diphenhydramine or equivalent, and methylprednisolone or equivalent). 18. The estimated glomerular filtration rate calculated according to the MDRD formula was <30mL/min/1.73m². 19. Blood tests performed at screening meet any of the following criteria: − Hemoglobin < 7.5 g/dL − Neutrophils < 1200/mm3 − Platelets < 110 × 109/L − Eosinophilic count > 3000/mm3 − Prothrombin time > 1.2 x upper limit of normal (ULN); However, subjects receiving anticoagulant therapy for atrial fibrillation with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2 x ULN − total immunoglobulin < 600mg/dL are not excluded − The number of CD19+B cells < 40 cells /μL during screening; This exclusion value is repeatable. 20. The subject has the following abnormal liver function test results in the absence of hepatobiliary IgG4-RD activity: − Aspartate aminotransferase (AST) > 2 x ULN − Alanine aminotransferase (ALT) > 2 x ULN − Total bilirubin (TBL) > 2 × ULN, Screening liver function tests may be repeated prior to randomization to allow outliers due to hepatobiliary IgG4-RD activity to respond to GC therapy. 21. Based on patient records, anti-neutrophil cytoplasmic antibodies (ANCA) targeting protease 3 or myeloperoxidase are known to be positive. 22. A history of alcohol or drug use that investigators believe may affect patient safety or visit compliance, or interfere with safety or other study evaluations. 23. There was clinically significant active infection at the time of randomization (if within the screening time window, IP administration could be delayed until recovery, otherwise subjects could be resold). 24. Is participating in any clinical trial that requires the use of any drug intervention.

研究实施时间：

Study execute time：

从 From 2023-08-31 00:00:00至 To 2027-08-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2023-08-31 00:00:00 至 To 2026-08-31 00:00:00

干预措施：

Interventions：

组别：	泰它西普治疗组	样本量：	20
Group：	Titacercept group	Sample size：	20
干预措施：	激素+泰它西普	干预措施代码：
Intervention：	GCs+titacercept	Intervention code：

组别：	对照组	样本量：	20
Group：	Control group	Sample size：	20
干预措施：	激素	干预措施代码：
Intervention：	GCs	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)：
Country：	China	Province：	Hubei	City：
单位(医院)：	华中科技大学同济医学院附属同济医院	单位级别：	三甲
Institution hospital：	Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	至疾病复发时间	指标类型：	主要指标
Outcome：	Time to disease recurrence	Type：	Primary 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、严重不良事件和特别关注不良事件的发生率	指标类型：	次要指标
Outcome：	Incidence of adverse events, serious adverse events, and adverse events of particular concern	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	年化复发率	指标类型：	次要指标
Outcome：	Annual recurrence 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：	在第52 周时达到无复发完全缓解的受试者比例	指标类型：	次要指标
Outcome：	The proportion of complete remission at week 52	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	至观察期内研究者首次用于新发或加重的疾病活动（无论是否被临床专业医师确定为复发）治疗的开始时间。	指标类型：	次要指标
Outcome：	The time to the start of the investigator's first treatment for new or aggravated disease activity (whether or not determined to be recurrent by a clinical professional) during the observation period.	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	糖皮质激素用量	指标类型：	次要指标
Outcome：	Glucocorticoid dosage	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：

正在进行

Recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	70	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）：

由不接触受试者的统计师将使用R语言"randomizr"包将40名患者进行1：1随机分组，并按照患者入院的顺序依次入组。T代表泰它西普治疗组，C代表安慰剂组，治疗信息一旦决定，将不接受任何更改。其他人，如研究调查人员、父母、患者和统计分析师，将对治疗条件完全不知情。任何不良反应或身体不适将在每次随访时记录。只有当参与者经历严重的不良事件时，上述个人才会被告知关于治疗的信息，然后独立的调查者将披露该参与者的当前治疗。

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

A statistician use the R "randomizr" package to randomly group 40 patients 1:1 according to the order in which they were admitted. "T" stands for the treatment group, "C" for the placebo group, and no changes will be accepted once the treatment information has been decided. Others, such as study investigators, parents, patients, and statistical analysts, will be completely unaware of the treatment conditions. Any adverse reactions or physical discomfort will be recorded at each follow-up visit. Only if the participant experiences a serious adverse event will the above individuals be informed about the treatment, and then an independent investigator will disclose the participant's current treatment.

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：	本研究采用双盲设计，负责疾病活动度评估的研究者和被试者均盲于分组。药品有与设盲编码一一对应的编码。在分发药品时，仅提供研究对象序号和设盲编码。此过程有相应的编盲记录并封存，由研究主要负责人保存，非必要时不得拆阅。
Blinding：	A double-blind design was used in this study, in which both investigators and subjects were blind in the assessment of disease activity. The drug has a code corresponding to the blind code. When distributing drugs, only the serial number of the study subject and the blind code are provided. This process has the corresponding compilation record and sealed by the main person in charge of the research, not open when necessary.
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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和EDC
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	CRF and EDC
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：	2023-08-23 09:04:54