ChiCTR2500097173 版本V1.0 版本创建时间2025/02/13 15:30:40 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：

ChiCTR2500097173 

最近更新日期：

Date of Last Refreshed on：

2025-02-13 15:30:29 

注册时间：

Date of Registration：

2025-02-13 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

评价注射用重组人白介素-1受体拮抗剂在痛风性关节炎间歇期患者中的安全性、药代动力学特征的Ⅰ期临床试验

Public title：

Phase I clinical trial to evaluate the safety and pharmacokinetic characteristics of a recombinant human interleukin-1 receptor antagonist for injection in patients with intermittent gouty arthritis

注册题目简写：

English Acronym：

研究课题的正式科学名称：

评价注射用重组人白介素-1受体拮抗剂在痛风性关节炎间歇期患者中的安全性、药代动力学特征的Ⅰ期临床试验

Scientific title：

Phase I clinical trial to evaluate the safety and pharmacokinetic characteristics of a recombinant human interleukin-1 receptor antagonist for injection in patients with intermittent gouty arthritis (protocol number: UA007-GT01)

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：

戴晓敏 

研究负责人：

姜林娣 

Applicant：

Xiaomin Dai 

Study leader：

Lindi Jiang  

申请注册联系人电话：

Applicant telephone：

+86 21 6404 1990

研究负责人电话：

Study leader's telephone：

+86 21 6404 1990

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：

dai.xiaomin@zs-hospital.sh.cn

研究负责人电子邮件：

Study leader's E-mail：

jiang.lindi@zs-hospital.sh.cn

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：

上海市徐汇区枫林路180号

研究负责人通讯地址：

上海市徐汇区枫林路180号

Applicant address：

180 Fenglin Road, Xuhui District, Shanghai

Study leader's address：

180 Fenglin Road, Xuhui District, Shanghai

申请注册联系人邮政编码：

Applicant postcode：

201203

研究负责人邮政编码：

Study leader's postcode：

201203

申请人所在单位：

复旦大学附属中山医院

Applicant's institution：

Zhongshan Hospital Affiliated to Fudan University

研究负责人所在单位：

复旦大学附属中山医院

Affiliation of the Leader：

Zhongshan Hospital Affiliated to Fudan University

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

2021-080R

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：

复旦大学附属中山医院伦理委员会

Name of the ethic committee：

Zhongshan Hospital Affiliated to Fudan University Ethics Committee

伦理委员会批准日期：

Date of approved by ethic committee：

2021-06-29 00:00:00

伦理委员会联系人：

杨梦婕

Contact Name of the ethic committee：

Mengjie Yang

伦理委员会联系地址：

上海市徐汇区枫林路180号

Contact Address of the ethic committee：

No. 180, Fenglin Road, Xuhui District, Shanghai

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 21 3367 6001

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：

复旦大学附属中山医院

Primary sponsor：

Zhongshan Hospital Affiliated to Fudan University

研究实施负责（组长）单位地址：

复旦大学附属中山医院

Primary sponsor's address：

Zhongshan Hospital Affiliated to Fudan University

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

上海

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

祐森健恒（上海）生物医药有限公司

具体地址：

浦东新区张衡路666弄1号楼207B室

Institution
hospital：

Usynova Pharmaceuticals Ltd.

Address：

Room 1-207, 666 Zhangheng Road, Pudong New Area

经费或物资来源：

祐森健恒（上海）生物医药有限公司

Source(s) of funding：

Usynova Pharmaceuticals Ltd.

Target disease：

Gouty Arthritis

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 I期临床试验 

Study phase：

1

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

1.评价UA007在痛风性关节炎间歇期患者中的安全性； 2.评价UA007在痛风性关节炎间歇期患者中的PK特征；  

Objectives of Study：

1. To evaluate the safety of UA007 in patients with intermittent gouty arthritis; 2. To evaluate the PK characteristics of UA007 in patients with intermittent gouty arthritis;

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.年龄为18-65周岁，性别不限； 2.体重≥50kg,且BMI在19-28kg/m^2范围内，包含两端； 3.符合痛风性关节炎诊断标准，且处于间歇期。详见ACR/EULAR2015痛风痛风分类标准（见附录1）； 4.研究期间愿意采用非激素性避孕措施； 5.理解并自愿签署知情同意书。

Inclusion criteria

1. Age is 18-65 years old, gender is not limited; 2. Weight >= 50kg, and BMI is in the range of 19-28kg/m^2, including both ends; 3. Meets the diagnostic criteria for gouty arthritis and is in the intermittent period. See ACR/EULAR 2015 Gout Classification Criteria (see Appendix 1); 4. Willingness to use non-hormonal contraception during the study; 5. Understand and voluntarily sign the informed consent form.

排除标准：

1. 对研究药物或研究药物中的任何成份过敏，或为过敏体质者； 2. 试验药物给药前使用了以下任何一种药物或治疗： 1） 给药前1个月内接受过研究药物类似结构或类似机理的药物治疗（如TNF-α、IL-1β、IL-6抑制剂）； 2） 给药前3个月内使用过已知具有较强的免疫抑制或免疫调节作用的药物（如他克莫司、雷公藤、糖皮质激素等）者； 3） 给药前2天吸烟、饮酒、或食用含高嘌呤类食物或咖啡因的食物饮料；剧烈运动；或有其他影响药物吸收、分布、代谢、排泄等因素者； 4） 受试者在给药前未服用降尿酸药（苯溴马隆、别嘌醇、非布司他等），而计划在研究期间使用者；在给药前服降尿酸药，不能稳定使用至少1个月及以上且血尿酸不能处在稳定期者；或1月内发生痛风急性发作者； 5） 给药前1个月内使用秋水仙碱、非甾体抗炎药（Nonsteroidal Anti-inflammatory Drugs，NSAIDs）药物治疗或预防痛风急性发作者； 3. 有以下任何一种疾病的病史或证据： 1） 有除痛风外的任何全身性炎症性疾病，包括但不局限于系统性红斑狼疮、幼年慢性关节炎、脊椎关节病、克罗恩病、溃疡性结肠炎、银屑病关节炎、活动性血管炎； 2） 给药前6个月内出现过失代偿性心力衰竭（纽约心脏病协会分级为III和IV）、不稳定性心绞痛、中风或短暂性脑缺血发作、心肌梗死、持续性且有临床意义的心律失常、进行过冠状动脉旁路移植术或经皮冠状动脉介入术； 3） 恶性肿瘤或恶性血液病病史； 4） 给药前3个月内接种过活疫苗或者到过疫区； 5） 筛选时患有症状性单纯疱疹； 6） 有结核（TB）病史者，或与活动性结核患者有家庭内接触且没有接受过适当及有记录的TB预防治疗者； 7） 患有血液恶液质或任何可引起溶血或红细胞不稳定的疾病； 8） 有活动性或复发性消化性溃疡者； 9） 给药前1个月内接受过大手术且研究者认为不适合接受试验药物； 10）给药前3个月内献血量>= 400 ml； 11） 给药前参加过任何药物或医疗器械的临床试验者（含安慰剂组），研究结束未超过30天，或未超过研究药物的5个半衰期（采用30天和5个半衰期中时间较长者）； 12）给药前2周内有感染性疾病且接受全身性抗生素治疗； 13）严重精神或神经系统疾病； 14）各种原因引起的继发性痛风，包括但不限于如下几种： ? 细胞增殖类疾病，包括白血病、淋巴瘤、骨髓瘤、红细胞增多症等原发疾病； ? 细胞破坏性疾病，包括溶血、烧伤、外伤、化疗、放疗、过量运动等原因引起； ? 高血压肾病、慢性肾炎、血管炎性肾炎、糖尿病肾病、红斑狼疮等疾病导致的肾功能不全； ? 其他疾病，如自身免疫性疾病、酸中毒等； ? 药物原因，如氢氯噻嗪、柳酸盐类、吡嗪酰胺等，以及一些利尿类药物会造成尿酸排泄减少，从而继发痛风； 15）有心血管、呼吸系统、肝脏、肾脏、消化道、免疫、血液、内分泌、代谢（如糖尿病、高脂血症等）等疾病，且经研究者判断可能影响药物的吸收、分布、代谢和排泄、或干扰结果评价者； 4. 筛选时有任何一项实验室检查指标符合下列标准： 1） 血红蛋白（男性）＜10.0 g/dL（100.0 g/L），或（女性）＜9.0 g/dL（90.0 g/L）； 2） 红细胞压积（HCT）＜32%； 3） 白细胞数＜4.0×109/L； 4） 中性粒细胞数＜2×109/L； 5） 血小板计数＜100×109/L； 6） AST或ALT＞2倍ULN； 7） 总胆红素＞2倍ULN； 8） 血尿酸＞535 μmol/L； 9） 估算肾小球滤过率（eGFR）＜60 ml/min； 10）乙肝表面抗原、丙肝抗体、HIV抗体、梅毒抗体检查阳性者；乙肝e抗原阳性者；乙肝表面抗原阴性而乙肝核心抗体阳性者； 11） 研究者认为可能对本研究结果评价产生干扰的任何有临床意义的实验室异常值； 5. 心电图检查QTc＞450 ms者； 6. 妊娠或哺乳期女性；试验期间及试验结束后6个月内不愿采取可靠避孕措施的育龄期女性或男性； 7. 不适合静脉采血； 8. 嗜烟（每日抽烟10支以上）或嗜酒[女性1天摄入的酒精量超过15 g，男性超过25 g（15 g酒精相当于450 ml啤酒、150 ml葡萄酒或50 ml低度白酒），每周超过两次]者或药物滥用史者； 9. 研究者认为存在任何可能影响本研究进行或结果评价的其他因素而不适合参加本临床试验

Exclusion criteria：

1. Allergic to the study drug or any ingredient in the study drug, or allergic to the constitution; 2. Before administration of the test drug, any of the following drugs or treatments were used: 1) those who received drug therapy with a similar structure or mechanism of the study drug (such as TNF-α, IL-1β, IL-6 inhibitors) within 1 month before administration; 2) those who used drugs known to have strong immunosuppressive or immunomodulatory effects (such as tacrolimus, tripterygium, glucocorticoid, etc.) within 3 months before administration; 3) those who smoked, drank alcohol, or ate foods and beverages containing high purine or caffeine; strenuous exercise; or those who had other factors affecting drug absorption, distribution, metabolism, excretion, etc.; 4) the subjects did not take uric acid lowering drugs (phenylbromide) before administration Malone, allopurinol, febustat, etc.), and plan to use it during the study period; those who take uric acid lowering drugs before administration, cannot be used stably for at least 1 month and the blood uric acid cannot be in a stable period; or those who experience an acute attack of gout within 1 month; 5) Those who use colchicine and nonsteroidal anti-inflammatory drugs (NSAIDs) within 1 month before administration to treat or prevent an acute attack of gout; 3. A history or evidence of any of the following conditions: 1) any systemic inflammatory disease other than gout, including but not limited to systemic lupus erythematosus, juvenile chronic arthritis, spondyloarthropathy, Crohn's disease, ulcerative colitis, psoriatic arthritis, active vasculitis; 2) a history of decompensated heart failure (New York Heart Association classification III and IV), unstable angina pectoris, stroke or transient ischemic attack, myocardial infarction, persistent and clinically significant arrhythmia, coronary artery bypass grafting or percutaneous coronary intervention; 3) a history of malignancy or hematologic malignancy; 4) a history of malignancy within 3 months prior to administration Have received a live vaccine or been to an affected area; 5) Symptomatic herpes simplex at the time of screening; 6) Have a history of tuberculosis (TB), or have family contact with an active TB patient who has not received appropriate and documented TB prophylaxis; 7) Have blood cachexia or any disease that can cause hemolysis or red blood cell instability; 8) Have active or recurrent peptic ulcer; 9) Have undergone major surgery within 1 month before administration and the investigator does not consider it suitable to receive the test drug; 10) Donate blood >= 400 ml within 3 months before administration; 11) Have participated in a clinical trial of any drug or medical apparatus before administration (including placebo group) The end of the study did not exceed 30 days, or did not exceed the 5 half-lives of the study drug (using 30 days and the longer of the 5 half-lives); 12) Infectious diseases and systemic antibiotic treatment within 2 weeks before administration; 13) Severe mental or nervous system diseases; 14) Secondary gout caused by various reasons, including but not limited to the following: cell proliferation diseases, including leukemia, lymphoma, myeloma, polycythemia and other primary diseases; cell destructive diseases, including hemolysis, burns, trauma, chemotherapy, radiotherapy, excessive exercise and other reasons; hypertensive nephropathy, chronic nephritis, vasculitic nephritis, diabetic nephropathy, lupus erythematosus and other diseases caused by renal insufficiency; other Diseases, such as autoimmune diseases, acidosis, etc.; drug causes, such as hydrochlorothiazide, salicates, pyrazinamides, etc., and some diuretic drugs can cause reduced uric acid excretion, resulting in secondary gout; 15) have cardiovascular, respiratory, liver, kidney, digestive tract, immune, blood, endocrine, metabolic (such as diabetes, hyperlipidemia, etc.) diseases, and may affect the absorption, distribution, metabolism and excretion of drugs, or interfere with the evaluation of results as judged by researchers; 4. At the time of screening, any of the laboratory test indicators met the following criteria: 1) hemoglobin (male) < 10.0 g/dL (100.0 g/L), or (female) < 9.0 g/dL (90.0 g/L); 2) hematocrit (HCT) < 32%; 3) white blood cell number < 4.0 × 10^9/L; 4) neutrophil number < 2 × 10^9/L; 5) platelet count < 100 × 109/L; 6) AST or ALT > 2 times ULN; 7) total bilirubin > 2 times ULN; 8) blood uric acid > 535 μmol/L; 9) estimated glomerular filtration rate (eGFR) < 60 ml/min; 10) Hepatitis B surface antigen, hepatitis C antibody, HIV antibody, syphilis antibody test positive; Hepatitis B e antigen positive; Hepatitis B surface antigen negative and hepatitis B core antibody positive; 11) any clinically significant laboratory abnormalities that the investigator believes may interfere with the evaluation of the results of this study; 5. Electrocardiogram QTc > 450 ms; 6. Pregnant or lactating women; women of childbearing age or men who do not want to take reliable contraceptive measures during the trial and within 6 months after the end of the trial; 7. Not suitable for intravenous blood collection; 8. Smoking (more than 10 cigarettes per day) or alcohol addiction [women consume more than 15 g of alcohol in 1 day, men consume more than 25 g (15 g of alcohol is equivalent to 450 ml of beer, 150 ml of wine or 50 ml of low Baijiu), more than twice a week] or drug abuse history; 9. The investigator believes that there are any other factors that may affect the conduct of this study or the evaluation of results, making it inappropriate to participate in this clinical trial

研究实施时间：

Study execute time：

从 From 2021-01-29 00:00:00至 To 2022-10-29 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2021-10-25 00:00:00 至 To 2022-01-12 00:00:00  

干预措施：

Interventions：

组别：

UA007组

样本量：

8

Group：

UA007 Group

Sample size：

干预措施：

给予受试者UA007 90 mg（3 ml无菌注射用水配制），单次肌肉（臀大肌）注射

干预措施代码：

Intervention：

Subjects were administered UA007 90 mg (prepared with 3 ml of sterile water for injection) with a single intramuscular (gluteus maximus) injection

Intervention code：

组别：

安慰剂组

样本量：

2

Group：

placebo group

Sample size：

干预措施：

给予受试者安慰剂生理盐水3 ml，单次肌肉（臀大肌）注射。

干预措施代码：

Intervention：

Subjects were given 3 ml of placebo saline with a single intramuscular (gluteus maximus) injection.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 上海市 

市(区县)：

  

Country：

china 

Province：

shanghai 

City：

 

单位(医院)：

复旦大学附属中山医院  

单位级别：

三甲 

Institution
hospital：

Zhongshan Hospital Affiliated to Fudan University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

药代动力学

指标类型：

主要指标

Outcome：

Pharmacokinetics

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：

结束

/Completed

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 65 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）：

简单随机 在SAS 9.4统计软件PROC PLAN过程中，根据事先定义的随机化参数，产生一份治疗分配表（即随机编码表），将各个受试者随机分入试验组或安慰剂组。受试者的随机号的命名规则定义为从小到大的三位数字001~010。药物编号的命名规则定义为从小到大的三位数字001~010，与受试者随机号一一对应。

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

Simple randomization. In the process of SAS 9.4 statistical software PROC PLAN, a treatment allocation table (ie, a randomized coding table) is generated according to the randomized parameters defined in advance, and each subject is randomly assigned to the trial group or the placebo group. The naming rules for the random number of the subject are defined as three digits 001~ 010 from small to large. The naming rules for the drug number are defined as three digits 001~ 010 from small to large, which correspond one to one with the random number of the subject.

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。由独立的统计人员去到祐森健恒生物医药（上海）有限公司按本研究的盲底进行药物编盲。随机抽取24瓶UA007，分别为8瓶试验药物，8瓶替补药物，8瓶备用药物。在药瓶身上贴上一张药物编号标签，药物编号将与受试者随机号一一对应。药物编盲完成后，将所有药品同6张安慰剂药物标签放回原始的药盒中，并在药盒外部贴上封条，填写编盲记录。过程由不参与本试验的工作人员进行编盲质控，编盲空间独立，无其他人员在场，保证药物编码信息处于盲态。

Blinding：

Double blinded. An independent statistician went to Yusen Jianheng Biopharmaceutical (Shanghai) Co., Ltd. to blind the drug according to the blind bottom of this study. 24 bottles of UA007 were randomly selected, which were 8 bottles of experimental drug, 8 bottles of replacement drug, and 8 bottles of backup drug. A drug number label was attached to the bottle, and the drug number would correspond to the random number of the subject. The numbers were 001~ 005, 007, 008, 010, 011~ 015, 017, 018, 020; 021~ 025, 027, 028, 030. At the same time, 6 placebo drug labels were prepared, and the numbers were 006, 009, 016, 019, 026, 029. After the drug blinding was completed, put all the drugs back in the original medicine box with 6 placebo drug labels, and affix a seal on the outside of the medicine box to fill in the blinding record. The blinding process was controlled by the staff who did not participate in the experiment, and the blinding space was independent, and no other personnel were present to ensure that the drug coding information was blinded.

是否共享原始数据：

IPD sharing

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）：

发表文章后；邮件联系项目负责人dai.xiaomin@zs-hospital.sh.cn. 国家生物信息中心 https://ngdc.cncb.ac.cn/gsub/

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

After publishing the paper; Contact the project leader via email: dai.xiaomin@zs-hospital.sh.cn. China National center for Bioinformation (https://ngdc.cncb.ac.cn/gsub/)

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：

（1）研究者必须保证数据真实、完整、准确。 （2）电子病历报告表（eCRF）：本研究将采用EDC系统进行数据的采集和管理。 （3）每次访视结束后，研究者或其授权的CRC应及时把所需信息录入EDC系统中。每一受试者观察疗程结束后，应在尽快将原始记录中相关信息以数据形式准确记录在“电子病例报告表”中，发现问题及时处理并记录。 （4）筛选失败的病例也需录入EDC系统中，录入内容应包括受试者人口学资料、筛败的原因、相应的检查和化验单或原始记录。

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

1. Investigators must ensure that the data are true, complete and accurate. 2. Electronic Medical Record Report Form (eCRF): This study will use EDC system for data collection and management. 3. After each visit, the investigator or authorized CRC should timely input the required information into the EDC system. After the end of the observation visit for each subject, the relevant information in the original records should be accurately recorded in the form of data in the "electronic case Report Form" as soon as possible, and the problems found should be handled and recorded in time. 4. Failed screening cases should also be input into the EDC system, which should include demographic data of subjects, reasons for screening failure, corresponding examinations and laboratory tests or original records.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2025-02-13 15:30:29