ChiCTR2500107351 版本V1.0 版本创建时间2025/08/08 18:10:25 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：

ChiCTR2500107351 

最近更新日期：

Date of Last Refreshed on：

2025-08-08 18:10:21 

注册时间：

Date of Registration：

2025-08-08 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

RGL-236注射液在膝骨关节炎受试者中单、多次给药的安全性、耐受性、免疫原性、药代动力学特征及初步有效性研究——一项开放标签、剂量递增的探索性临床试验

Public title：

A study on the safety, tolerability, immunogenicity, pharmacokinetic characteristics and preliminary efficacy of RGL-236 Injection in single and multiple dosing in patients with knee osteoarthritis: An open-label, dose-escalation exploratory clinical trial

注册题目简写：

English Acronym：

研究课题的正式科学名称：

RGL-236注射液在膝骨关节炎受试者中单、多次给药的安全性、耐受性、免疫原性、药代动力学特征及初步有效性研究——一项开放标签、剂量递增的探索性临床试验

Scientific title：

A study on the safety, tolerability, immunogenicity, pharmacokinetic characteristics and preliminary efficacy of RGL-236 Injection in single and multiple dosing in patients with knee osteoarthritis: An open-label, dose-escalation exploratory 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：

王昊 

研究负责人：

刘璠 

Applicant：

Hao Wang 

Study leader：

Fan Liu 

申请注册联系人电话：

Applicant telephone：

+86 188 1750 7266

研究负责人电话：

Study leader's telephone：

+86 139 0148 2027

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：

hao.wang@regenelead.com

研究负责人电子邮件：

Study leader's E-mail：

liufan19575@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：

上海市浦东新区桂桥路255号

研究负责人通讯地址：

江苏省南通市崇川区西寺路20号

Applicant address：

No. 255 Guiqiao Road, Pudong New Area, Shanghai

Study leader's address：

No. 20, Xisi Road, Chongchuan District, Nantong City, Jiangsu Province

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：

上海瑞宏迪医药有限公司

Applicant's institution：

Shanghai Regenelead Theraples,Co,Ltd.

研究负责人所在单位：

南通大学附属医院

Affiliation of the Leader：

Affiliated Hospital of Nantong 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：

2025-K167-02

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：

南通大学附属医院伦理委员会

Name of the ethic committee：

Ethics Committee of the Affiliated Hospital of Nantong University

伦理委员会批准日期：

Date of approved by ethic committee：

2025-07-14 00:00:00

伦理委员会联系人：

张妞

Contact Name of the ethic committee：

Niu Zhang

伦理委员会联系地址：

江苏省南通市西寺路20号南通大学附属医院2号楼8楼

Contact Address of the ethic committee：

8th Floor, Building 2, Nantong University Affiliated Hospital, No. 20, Xisi Road, Nantong City, Jiangsu Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 513 8505 2390

伦理委员会联系人邮箱：

Contact email of the ethic committee：

lunlib@126.com

研究实施负责（组长）单位：

南通大学附属医院

Primary sponsor：

Affiliated Hospital of Nantong University

研究实施负责（组长）单位地址：

江苏省南通市崇川区西寺路20号

Primary sponsor's address：

No. 20, Xisi Road, Chongchuan District, Nantong City, Jiangsu Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

江苏省

市(区县)：

南通市

Country：

China

Province：

Jiangsu

City：

Nantong

单位(医院)：

南通大学附属医院

具体地址：

江苏省南通市崇川区西寺路20号

Institution
hospital：

Affiliated Hospital of Nantong University

Address：

No. 20, Xisi Road, Chongchuan District, Nantong City, Jiangsu Province

经费或物资来源：

上海瑞宏迪医药有限公司

Source(s) of funding：

Shanghai Regenelead Theraples,Co,Ltd.

Target disease：

Knee osteoarthritis

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：

单臂 

Study design：

Single arm 

研究目的：

评估在膝骨关节炎受试者中单、多次关节腔内注射RGL-236的安全性和耐受性  

Objectives of Study：

To evaluate the safety and tolerability of single and multiple intra-articular injections of RGL-236 in subjects with knee osteoarthritis

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. 受试者必须能够理解和与研究者沟通，能够遵守研究要求，并且必须在进行任何研究评估前提供已签字并注明日期的书面知情同意书。 2. 年龄为55 ~75 岁（含两端）的男性和女性。 3. 身体质量指数（BMI）< 30 kg/m^2。 4. 研究侧膝关节诊断为原发性膝骨关节炎（根据2018年版《中国骨关节炎诊疗指南》）。 5. 研究侧膝骨关节炎主要累及内侧胫股间室，Kellgren-Lawrence（K-L）放射学分级（立位）为2或3级，且伴随疼痛症状。 6. 筛选期内的两次研究侧膝关节WOMAC疼痛评分的平均值为15 ~ 45分（共50分），其中第一项“在平地行走的时候”平均值≥5分（共10分）

Inclusion criteria

1. The subjects must be able to understand and communicate with the researchers, comply with the research requirements, and must provide a signed and dated written informed consent form before any research evaluation is conducted. Men and women aged 55 to 75 (including both ends). 3. Body Mass Index (BMI) < 30 kg/m^2. 4. The knee joint on the study side was diagnosed with primary knee osteoarthritis (according to the 2018 edition of the "Chinese Guidelines for the Diagnosis and Treatment of Osteoarthritis"). 5. The lateral knee osteoarthritis mainly involved the medial tibiofemoral compartment, with a Kellgren-Lawrence (K-L) radiological grade (upright) of 2 or 3, and was accompanied by pain symptoms. 6. The average WOMAC pain score of the knee joint on the study side during the screening period was 15 to 45 points (a total of 50 points), among which the average score of the first item "when walking on flat ground" was >= 5 points (a total of 10 points).

排除标准：

1. 非研究侧膝骨关节炎的K-L放射学分级为4级。 2. 研究侧膝关节严重的膝内/外翻畸形。 3. 筛选前4周内进行研究侧膝关节电疗法、针灸、玻璃酸钠关节腔注射等治疗；或筛选前3个月进行过研究侧膝关节腔注射中短效皮质类固醇激素等药物，或筛选前6个月内关节腔注射富血小板血浆或长效皮质类固醇激素。 4. 筛选前4周内或筛选期间研究侧膝关节有中-重度炎症的临床表现（即发红、发热、积液）。 5. 既往曾对研究侧膝关节腔内进行过手术或计划在试验期间进行膝关节手术。 6. 存在由临床评估或影像学证实的其他膝关节病理表现，包括软骨下不全骨折、骨折（筛选前6个月内的急性或亚急性骨折）或骨挫伤、骨坏死、恶性骨髓浸润、实体瘤和/或髌股关节发育不良。 7. 研究侧膝关节注射位点有局部注射禁忌症，例如开放性创伤、银屑病病灶、局部感染等；或研究者判断无法进行膝关节注射的全身疾病或状况，例如凝血功能障碍性疾病（血友病、冯维勒布兰德氏病、因子X缺乏等）、需进行抗凝治疗的等。 8. 存在可能混淆对膝骨关节炎相关疼痛评估的其他疼痛情况，如：可能累及关节的全身性疾病、神经疾病、累及膝关节的佩吉特氏病、神经根病型腰椎压迫引起的局部疼痛以及其他任何可能混淆有效性评估的疼痛情况；或在筛选期前5个药物半衰期或2周内使用中枢镇痛药物（例如曲马多），麻醉性镇痛药（例如吗啡、杜冷丁和其他阿片类药物）等。 9. 筛选时已知其他关节或软骨疾病，自身免疫性疾病伴炎症性关节炎（包括但不限于类风湿关节炎、银屑病关节炎、强直性脊柱炎、系统性红斑狼疮）、晶体性关节炎（痛风、假性痛风性关节炎）、反应性关节炎、活动性急性或慢性膝关节感染或既往膝关节感染、全身性软骨疾病、全身性结缔组织疾病。 10. 筛选时既往有恶性肿瘤病史，或有任何器官系统的恶性肿瘤病史。 11. 已知有任何活动性感染，包括注射部位皮肤感染或膝关节感染或可能损害免疫系统的感染（如HIV感染或活动性HBV感染或HCV感染或梅毒等）。 活动性HBV感染：筛选时乙肝表面抗原（HbsAg）阳性且HBV-DNA病毒载量大于当地医疗机构正常参考范围的上限。 12. 实验室检查异常： 1) 血红蛋白 < 80 g/L或血小板＜100×109/L； 2) 丙氨酸氨基转移酶（ALT）或天门冬氨酸氨基转移酶（AST）＞2.5×正常上限（ULN），总胆红素＞1.5×ULN； 3) 血肌酐（Cr）＞1.5×ULN； 4) 空腹血糖 > ULN； 5) 糖化血红蛋白A1c（HbA1c）>6.5%。 13. 筛选期内未得到良好控制的重大慢性疾病，如未控制的高血压（治疗后收缩压≥180mmHg或舒张压≥110mmHg）、需要干预的严重心律失常、慢性心力衰竭（纽约心脏病协会（NYHA）分级为III 或IV 级）。 14. 筛选前3个月内，发生脑梗死（除外腔隙性梗死）、脑出血、心肌梗死、不稳定性心绞痛的患者。 15. 筛选前3个月内有重大手术史或计划在研究期间进行重大手术。 16. 有对任何一种研究药物或其辅料或与其同类别药物有过敏史。 17. 既往有药物或酒精滥用史，或确诊有任何精神疾病。 18. 既往使用过基因细胞治疗（包括质粒DNA、RNA、基因改造的病毒、细菌或细胞以及基于基因编辑技术的产品等）或参与过基因细胞治疗相关的临床试验。 19. 筛选前3个月内参加过除基因细胞治疗产品以外其他药物干预的临床试验（除外筛选失败者），或者筛选时尚在药物5个半衰期以内（以时间更长者为准）。 20. 一般情况： 1) 不能正确描述症状和情绪/情感者； 2) 无法配合完成试验过程中相关检查和评估。 3) 不同意在研究期间和末次给药后6个月内采用高效避孕措施的男性或女性受试者； 4) 妊娠或哺乳期女性； 5) 研究者判定受试者依从性不佳或具有任何不宜参加此试验的因素，包括但不限于研究会使受试者处于不可接受的风险或可能干扰研究结果，或受试者功能状态差无法进行自我照顾。

Exclusion criteria：

1.The K-L radiological grade of knee osteoarthritis on the non-study side was grade 4. 2. Study severe genu varum/valgus deformity of the knee joint on the research side. 3. Within 4 weeks before screening, treatments such as electrotherapy, acupuncture, and intra-articular injection of sodium hyaluronate on the study side of the knee joint should be carried out. Or, medium and short-acting corticosteroid hormones or other drugs were injected into the knee cavity of the study side within 3 months before screening, or platelet-rich plasma or long-acting corticosteroid hormones were injected into the joint cavity within 6 months before screening. 4. Within 4 weeks before screening or during the screening period, there were clinical manifestations of moderate to severe inflammation in the knee joint of the study side (i.e., redness, fever, and effusion). 5. Has previously undergone surgery in the lumen of the knee joint on the study side or plans to perform knee joint surgery during the trial period. 6. There are other pathological manifestations of the knee joint confirmed by clinical assessment or imaging, including subchondral incomplete fractures, fractures (acute or subacute fractures within 6 months prior to screening), bone contusion, osteonecrosis, malignant bone marrow infiltration, solid tumors and/or patellofemoral dysplasia. 7. There are contraindications for local injection at the injection site of the knee joint on the study side, such as open trauma, psoriasis lesions, local infections, etc. Or systemic diseases or conditions that researchers determine cannot be used for knee joint injection, such as coagulation disorders (hemophilia, von Wille-Brandder's disease, factor X deficiency, etc.), and those requiring anticoagulant therapy, etc. 8. There are other pain conditions that may confuse the assessment of knee osteoarthritis-related pain, such as: systemic diseases that may involve the joint, neurological diseases, Paget's disease involving the knee joint, local pain caused by lumbar compression of radiculopathy type, and any other pain conditions that may confuse the assessment of effectiveness; Or use central analgesics (such as tramadol), narcotic analgesics (such as morphine, pethidine and other opioids), etc. within the first five drug half-lives or within two weeks before the screening period. 9. Other joint or cartilage diseases were known during screening. Autoimmune diseases with inflammatory arthritis (including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus), crystalline arthritis (gout, pseudo-gouty arthritis), reactive arthritis, active acute or chronic knee joint infection or previous knee joint infection, systemic cartilage diseases, systemic connective tissue diseases. 10. At the time of screening, there is a history of malignant tumors in the past, or a history of malignant tumors in any organ system. 11. It is known that there are any active infections, including skin infections at the injection site or knee joint infections or infections that may damage the immune system (such as HIV infection or active HBV infection or HCV infection or syphilis, etc.). Active HBV infection: Positive hepatitis B surface antigen (HbsAg) at screening and HBV-DNA viral load greater than the upper limit of the normal reference range of local medical institutions. 12. Abnormal laboratory tests: Hemoglobin < 80 g/L or platelets < 100×10^9/L; 2) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5× upper limit of normal (ULN), total bilirubin > 1.5×ULN; 3) Serum creatinine (Cr) > 1.5×ULN; 4) Fasting blood glucose > ULN; 5) Glycated hemoglobin A1c (HbA1c) >6.5%. 13. Major chronic diseases that were not well controlled during the screening period, such as uncontrolled hypertension (systolic blood pressure >= 180mmHg or diastolic blood pressure >= 110mmHg after treatment), severe arrhythmias requiring intervention, and chronic heart failure (New York Heart Association (NYHA) grade III or IV). 14. Patients who have experienced cerebral infarction (excluding lacunar infarction), cerebral hemorrhage, myocardial infarction, or unstable angina pectoris within 3 months prior to screening. 15. Have a history of major surgery within 3 months prior to screening or plan to undergo major surgery during the study period. 16. Have a history of allergy to any of the research drugs or their excipients or drugs of the same category. 17. There is a history of drug or alcohol abuse, or a confirmed diagnosis of any mental illness. 18. Have previously used gene and cell therapy (including plasmid DNA, RNA, genetically modified viruses, bacteria or cells, and products based on gene editing technology, etc.) or participated in clinical trials related to gene and cell therapy. 19. Having participated in clinical trials of drugs other than gene and cell therapy products within three months prior to screening (excluding those who failed the screening), or being within five half-lives of the drug at the time of screening (whichever is longer). 20. General situation: 1) Those who cannot accurately describe symptoms and emotions/feelings; 2) Unable to cooperate in completing relevant inspections and evaluations during the test process. 3) Male or female subjects who did not intend to use highly effective contraceptive measures during the study period and within 6 months after the last administration; 4) Pregnant or lactating women; 5) The researchers determined that the subjects had poor compliance or any factors that made them unsuitable for participating in this trial, including but not limited to factors that would put the subjects at an unacceptable risk or potentially interfere with the research results, or that the subjects were in a poor functional state and unable to take care of themselves.

研究实施时间：

Study execute time：

从 From 2025-06-30 00:00:00至 To 2026-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2025-08-08 00:00:00 至 To 2025-12-31 00:00:00  

干预措施：

Interventions：

组别：

单药治疗剂量递增

样本量：

9

Group：

Increase the dose of single-drug treatment

Sample size：

干预措施：

贝叶斯最优区间（BOIN）设计指导剂量递增

干预措施代码：

Intervention：

Bayesian optimal interval (BOIN) design was adopted to guide dose escalation

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 江苏省 

市(区县)：

  

Country：

China 

Province：

Jiangsu 

City：

 

单位(医院)：

南通大学附属医院 

单位级别：

三甲 

Institution
hospital：

Affiliated Hospital of Nantong University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

RGL-236的安全性和耐受性

指标类型：

主要指标

Outcome：

The safety and tolerance of RGL-236

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

RGL-236的药代动力学（PK）特征

指标类型：

次要指标

Outcome：

The pharmacokinetic (PK) characteristics of RGL-236

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

RGL-236的免疫原性

指标类型：

次要指标

Outcome：

The immunogenicity of RGL-236

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：

标本中文名：

尿液

组织：

Sample Name：

Urine

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：

关节腔液

组织：

Sample Name：

joint cavity fluid

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 55 岁 years
最大 Max age 75 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）：

无

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

N/A

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：

Blinding：

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）：

无

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

N/A

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：

Case Record Form

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：

  2025-08-08 18:10:21