ChiCTR2600121008 版本V1.0 版本创建时间2026/03/24 11:12:04 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：

 ChiCTR2600121008 

最近更新日期：

Date of Last Refreshed on：

 2026-03-24 11:11:41 

注册时间：

Date of Registration：

 2026-03-24 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

视网膜下注射AAV-nCas9和AAV-DIDA-CBE编辑VEGF基因治疗抗VEGF抗体耐药的AMD临床研究

Public title：

Clinical Study of Subretinal Injection of AAV-nCas9 and AAV-DIDA-CBE for Editing the VEGF Gene to Treat Anti-VEGF Antibody-Resistant AMD

注册题目简写：

English Acronym：

研究课题的正式科学名称：

视网膜下注射AAV-nCas9和AAV-DIDA-CBE编辑VEGF基因治疗抗VEGF抗体耐药的AMD临床研究

Scientific title：

Clinical Study of Subretinal Injection of AAV-nCas9 and AAV-DIDA-CBE for Editing the VEGF Gene in Anti-VEGF Antibody-Resistant Age-Related Macular Degeneration

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：

迟玮 

研究负责人：

迟玮 

Applicant：

Chi Wei 

Study leader：

Chi Wei 

申请注册联系人电话：

Applicant telephone：

 +86 17633909305

研究负责人电话：

Study leader's
telephone：

+86 13710616456

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：

 wc450250269@163.com

研究负责人电子邮件：

Study leader's E-mail：

 chiwei@mail.sysu.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：

广东省深圳市福田区泽田路18号

研究负责人通讯地址：

广东省深圳市福田区泽田路18号

Applicant address：

18 Zetian Road, Futian District, Shenzhen City, Guangdong Province

Study leader's address：

18 Zetian Road, Futian District, Shenzhen, Guangdong

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：

深圳市眼科医院

Applicant's institution：

Shenzhen Eye Hospital

研究负责人所在单位：

深圳市眼科医院

Affiliation of the Leader：

Shenzhen Eye 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：

 2026KYPJ015

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：

深圳市眼科医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Shenzhen Eye Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2026-03-10 00:00:00

伦理委员会联系人：

张晓铃

Contact Name of the ethic committee：

Zhang Xialing

伦理委员会联系地址：

广东省深圳市福田区泽田路18号

Contact Address of the ethic committee：

18 Zetian Road, Futian District, Shenzhen, Guangdong

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 755 23959627

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 szehec@126.com

研究实施负责（组长）单位：

深圳市眼科医院

Primary sponsor：

Shenzhen Eye Hospital

研究实施负责（组长）单位地址：

广东省深圳市福田区泽田路18号

Primary sponsor's address：

18 Zetian Road, Futian District, Shenzhen, Guangdong

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

广东省

市(区县)：

Country：

China

Province：

Guangdong

City：

单位(医院)：

深圳市眼科医院

具体地址：

广东省深圳市福田区泽田路18号

Institution
hospital：

Shenzhen Eye Hospital

Address：

18 Zetian Road, Futian District, Shenzhen, Guangdong

经费或物资来源：

蛋白质机器与生命过程调控;广东省基础与应用基础研究基金项目;深圳市科技创新局

Source(s) of funding：

National Natural Science Foundation of China;Guangdong Provincial Foundation for Fundamental and Applied Basic Research Fund Project;Shenzhen Municipal Science and Technology Innovation Bureau

研究疾病：

抗VEGF治疗耐药的湿性年龄相关性黄斑变性  

Target disease：

Wet age-related macular degeneration resistant to anti-VEGF therapy

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：

单臂 

Study design：

Single arm 

研究目的：

评估视网膜下注射AAV-nCas9和AAV-DIDA-CBE编辑VEGF基因治疗抗VEGF抗体耐药的AMD安全性及耐受性  

Objectives of Study：

Safety and Tolerability Assessment of Subretinal Injection of AAV-nCas9 and AAV-DIDA-CBE for VEGF Gene Editing in Anti-VEGF Antibody-Resistant AMD

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.诊断为新生血管性年龄相关性黄斑变性的患者，男女不限。
2.年龄在50岁至89岁之间。
3.研究眼既往抗VEGF治疗后，根据SD-0CT评估曾表现治疗有应答（注射后1 周，中心凹视网膜厚度较基线有减少，但减少≤50微米或中央液体改善≤30%）。
4.研究眼在筛选前8个月内接受抗VEGF药物玻璃体内注射，至少4次治疗表现应答不佳(注射后1周，中心凹视网膜厚度较基线增加和(或)BCVA与基线或治疗后最高BCVA相比丢失字母数＞5个)。
5.招募受试者最佳矫正视力（BCVA）在20/400至20/63之间（Snellen视力表，对应ETDRS字母数19-63个）。
6.双眼均符合入选条件，选择纳入视力较差眼。
7.研究眼须明确诊断为继发于AMD的黄斑中心凹下CNV。CNV病灶面积小于10个视盘面积，出血面积须小于病灶总面积的50%；
8.研究眼白内障程度不影响眼底的评估或为人工晶状体眼。
9.能够配合所有研究程序及研究期间的随访。
10.有生育能力的女性受试者，在筛选访视时尿妊娠试验为阴性，第8天血清妊娠检测结果须为阴性，且须同意在研究期间接受额外的妊娠检测。
11.有性生活者须同意自接受招募日起至载体给药后24周内，采取避孕措施；此后若需停止避孕，应与责任医师讨论后决定。
12.受试者须愿意并能够签署书面知情同意书。

Inclusion criteria

1. Patients diagnosed with neovascular age-related macular degeneration, regardless of gender. 2. Aged between 50 and 89 years old. 3. Following prior anti-VEGF therapy in the study eye, SD-OCT assessment indicated a prior therapeutic response (defined as a reduction in central retinal thickness of <=50 micrometres from baseline or improvement in central fluid of <=30% at one week post-injection). 4. Subjects had received intravitreal injections of anti-VEGF agents within the eight months preceding screening, demonstrating inadequate response to at least four treatments (defined as increased central retinal thickness at one week post-injection compared to baseline and/or a loss of >=5 letters in best-corrected visual acuity (BCVA) relative to baseline or the highest BCVA achieved during treatment). 5. Recruited subjects had best-corrected visual acuity (BCVA) ranging from 20/400 to 20/63 (Snellen chart, corresponding to ETDRS letters 19 to 63). 6. Both eyes meet the inclusion criteria; the eye with poorer vision is selected for inclusion. 7. The study must clearly diagnose subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD). The CNV lesion area must be less than 10 disc areas, and the haemorrhagic area must constitute less than 50% of the total lesion area. 8. The degree of cataract formation does not affect the assessment of the fundus or the fitting of an intraocular lens. 9. Able to comply with all research procedures and follow-up appointments during the study period. 10. Female subjects of childbearing potential must have a negative urine pregnancy test at the screening visit, a negative serum pregnancy test result on day 8, and must consent to additional pregnancy testing during the study period. 11. Participants who are sexually active must agree to use contraception from the date of recruitment until 24 weeks after carrier administration. Should contraception need to be discontinued thereafter, this should be decided following discussion with the responsible physician. 12. Subjects must be willing and able to sign a written informed consent form.

排除标准：

1.研究眼存在除AMD以外其他原因所致的CNV或黄斑水肿。
2.AMD病灶中出血面积≥50%，或研究眼黄斑中心凹下方出血面积＞1.0mm2。
3.存在任何可能阻碍研究眼视力改善的病变，例如中心凹区域的纤维化、萎缩或视网膜色素上皮撕裂。
4.研究眼存在活动性视网膜脱离，或既往有视网膜脱离病史。
5.研究眼存在晚期青光眼。
6.研究眼存在任何可能增加受试者风险、需在研究期间接受药物或手术干预以预防或治疗视力丧失，或干扰研究操作或评估的疾病（由研究者判断）。
7.招募前12周内研究眼曾接受过眼内手术，或10周内接受钇铝石榴石激光后囊切开术。
8.招募前6个月内，研究眼曾接受抗VEGF治疗除外的其他玻璃体内治疗（如玻璃体内糖皮质激素注射或试验用产品）。
9.招募时研究眼已置入植入物（人工晶状体除外）。
10.招募前5年内曾患需接受化疗和/或放疗的恶性肿瘤。局限性基底细胞癌除外。
11.入组前30天内或试验用产品5个半衰期内曾接受过试验用产品。
12.曾参与其他基因治疗研究。
13.既往接受过已知可致视网膜毒性的治疗，或当前正在接受可能影响视力或具有已知视网膜毒性的药物（例如氯喹或羟氯喹）。
14.研究眼存在可能干扰手术操作的眼部或眼周感染。
15.近6个月内发生过心肌梗死、脑血管意外或短暂性脑缺血发作。
16.存在未控制的高血压（收缩压＞180 mmHg，舒张压＞100 mmHg）。
17.正在同时接受可能干扰眼部手术操作或术后愈合的治疗（由研究者判断）。
18.已知对雷珠单抗或其成分物过敏，或既往对AAV类药物存在过敏反应（由研究者判断）。
19.患有严重、慢性或不稳定的内科或精神疾病，经研究者判断可能危及受试者安全，或影响其完成全部评估及随访。

Exclusion criteria：

1. Investigate the presence of choroidal neovascularisation or macular oedema caused by factors other than age-related macular degeneration. 2. The haemorrhagic area within the AMD lesion is >=50%, or the haemorrhagic area beneath the fovea centralis in the study eye exceeds 1.0 mm2. 3. Any pathological condition that may impede the improvement of visual acuity, such as fibrosis, atrophy, or retinal pigment epithelial detachment in the foveal region. 4. The eye under investigation exhibits active retinal detachment or a history of retinal detachment. 5. The eye exhibits signs of advanced glaucoma. 6. Investigate any existing conditions that may increase subject risk, necessitate pharmacological or surgical intervention during the study to prevent or treat vision loss, or interfere with study procedures or assessments (as determined by the investigator). 7. Subjects who had undergone intraocular surgery within the 12 weeks preceding recruitment, or who had received YAG laser posterior capsulotomy within the preceding 10 weeks. 8. Within the six months preceding recruitment, the study eye had received intravitreal treatment other than anti-VEGF therapy (such as intravitreal corticosteroid injections or investigational products). 9. At the time of recruitment, the eye under investigation must already have an implant (excluding intraocular lenses). 10. Recruitment excludes individuals who have had malignant tumours requiring chemotherapy and/or radiotherapy within the preceding five years. Excludes localised basal cell carcinoma. 11. Received the investigational product within 30 days prior to study entry or within five half-lives of the investigational product. 12. Has previously participated in other gene therapy research. 13. Previously received treatment known to cause retinal toxicity, or currently receiving medication that may affect vision or has known retinal toxicity (e.g., chloroquine or hydroxychloroquine). 14. Investigate whether any ocular or periorbital infections may interfere with surgical procedures. 15. Myocardial infarction, cerebrovascular accident, or transient ischaemic attack within the past six months. 16. Uncontrolled hypertension is present (systolic blood pressure > 180 mmHg, diastolic blood pressure > 100 mmHg). 17. Currently undergoing treatment concurrently that may interfere with ocular surgical procedures or postoperative healing (as determined by the investigator). 18. Known hypersensitivity to rituximab or any of its constituents, or a history of allergic reactions to AAV-based medicinal products (as determined by the investigator). 19. Suffering from severe, chronic, or unstable medical or psychiatric conditions which, in the investigator's judgement, may jeopardise the subject's safety or impair their ability to complete all assessments and follow-up.

研究实施时间：

Study execute time：

从 From 2026-04-01 00:00:00至 To 2027-06-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2026-04-01 00:00:00 至 To 2026-05-31 00:00:00

干预措施：

Interventions：

组别：

治疗组

样本量：

 6

Group：

Treatment group

Sample size：

干预措施：

视网膜下注射7.5×10^10 vg/眼的AAV-nCas9和AAV-DIDA-CBE

干预措施代码：

Intervention：

Subretinal injection of 7.5×10^10 vg/eye of AAV-nCas9 and AAV-DIDA-CBE

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 广东省 

市(区县)：

  

Country：

China

Province：

Guangdong

City：

单位(医院)：

 深圳市眼科医院 

单位级别：

 三级甲等 

Institution
hospital：

Shenzhen Eye Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

视网膜下注射24周内的不良事件的发生率

指标类型：

主要指标

Outcome：

Incidence of adverse events within 24 weeks of subretinal injection

Type：

Primary indicator

测量时间点：

视网膜下注射后1周、2周及术后每4周

测量方法：

根据常见不良事件评价标准（CTCAE）5.0版本进行眼部及全身不良反应1 级至 5 级的评估。

Measure time point of outcome：

One week, two weeks, and every four weeks after subretinal injection

Measure method：

Adverse reactions affecting the ocular system and systemic organs were graded from Grade 1 to Grade 5 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

指标中文名：

视网膜下注射随访48周的安全性

指标类型：

次要指标

Outcome：

Safety of subretinal injections at 48 weeks follow-up

Type：

Secondary indicator

测量时间点：

视网膜下注射后1周、2周及术后每4周

测量方法：

记录眼部及全身发生的不良事件

Measure time point of outcome：

One week, two weeks, and every four weeks after subretinal injection

Measure method：

Record adverse events occurring in the eye and throughout the body

指标中文名：

最佳矫正视力

指标类型：

次要指标

Outcome：

Best-corrected visual acuity

Type：

Secondary indicator

测量时间点：

视网膜下注射后1周、2周及术后每4周

测量方法：

使用ETDRS视力表测量患者双眼的最佳矫正视力，并记录字母数。

Measure time point of outcome：

One week, two weeks, and every four weeks after subretinal injection

Measure method：

Measure the patient's best-corrected visual acuity in both eyes using the ETDRS chart and record the number of letters.

指标中文名：

随访48周内补充抗VEGF-A注射的必要性

指标类型：

次要指标

Outcome：

The necessity of supplementary anti-VEGF-A injections during the 48-week follow-up period

Type：

Secondary indicator

测量时间点：

视网膜下注射后每4周

测量方法：

统计每位受试者补充抗VEGF-A注射的次数

Measure time point of outcome：

Every four weeks after subretinal injection

Measure method：

Count the number of anti-VEGF-A injections administered to each subject.

指标中文名：

前房水中VEGF蛋白的浓度

指标类型：

次要指标

Outcome：

Concentration of VEGF protein in the anterior chamber aqueous

Type：

Secondary indicator

测量时间点：

视网膜下注射后2周、24周及48周

测量方法：

酶联免疫吸附测定法检测不同时间点参与者的前房水中VEGF浓度

Measure time point of outcome：

Two weeks, 24 weeks and 48 weeks after subretinal injection

Measure method：

Enzyme-linked immunosorbent assay for detecting VEGF concentrations in the aqueous humour of participants at different time points

指标中文名：

中央视网膜厚度

指标类型：

次要指标

Outcome：

Central retinal thickness

Type：

Secondary indicator

测量时间点：

视网膜下注射后1周、2周及术后每4周

测量方法：

使用SD-OCT进行检测视网膜中心凹厚度的变化

Measure time point of outcome：

One week, two weeks, and every four weeks after subretinal injection

Measure method：

Using SD-OCT to detect changes in macular thickness

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

外周血

组织：

Sample Name：

Peripheral blood

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation after use  

Note：

标本中文名：

尿液

组织：

Sample Name：

urine

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation after use  

Note：

标本中文名：

前房水

组织：

Sample Name：

Anterior chamber fluid

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation 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 50 岁 years
最大 Max age 89 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)：

None

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：

无

Blinding：

None

是否共享原始数据：

IPD sharing

是Yes

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）：

网络平台

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

online platform

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：

采用统一的电子病例报告表进行数据采集，关键数据由双人核对后录入，录入完成后对比纠错，记录纠错过程。统计专家完成数据的逻辑性核查，异常值核查由研究者提供合理解释，无法解释的异常值需重新检测验证。纸质数据存档于本院GCP办公室专用档案柜，电子数据备份于院内安全服务器。

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

Data collection utilises a standardised electronic case report form. Key data undergoes double-entry verification before input, followed by cross-checking and error correction with documentation of the rectification process. Statistical specialists conduct logical data verification, with researchers providing reasonable explanations for outliers. Unexplained anomalies necessitate repeat testing for validation. Paper records are archived in the dedicated filing cabinet of the hospital's GCP office, whilst electronic data is backed up on secure internal servers.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2026-03-24 11:11:41