ChiCTR2300069823 版本V1.2 版本创建时间2026/03/26 08:17:00 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：

 ChiCTR2300069823 

最近更新日期：

Date of Last Refreshed on：

 2023-05-28 17:05:26 

注册时间：

Date of Registration：

 2023-03-27 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

Brolucizumab和其他抗VEGF藥物在應付新生血管型老年黃斑病變和息肉狀脈絡膜血管病變中的治療學和藥物基因組學 — 邁向精準醫學的深度學習研究

Public title：

Therapeutics and Pharmacogenetics of Brolucizumab and Other Anti-VEGF Agents in Treating Neovascular Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy – Deep Learning towards Precision Medicine

注册题目简写：

English Acronym：

研究课题的正式科学名称：

Brolucizumab和其他抗VEGF藥物在應付新生血管型老年黃斑病變和息肉狀脈絡膜血管病變中的治療學和藥物基因組學 — 邁向精準醫學的深度學習研究

Scientific title：

Therapeutics and Pharmacogenetics of Brolucizumab and Other Anti-VEGF Agents in Treating Neovascular Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy – Deep Learning towards Precision Medicine

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：

Ms Jennifer Tsoi 

研究负责人：

陳理佳教授 

Applicant：

Ms Jennifer Tsoi 

Study leader：

Prof Lijia Chen 

申请注册联系人电话：

Applicant telephone：

 +852 39435818

研究负责人电话：

Study leader's
telephone：

+852 39435810

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：

 jennifertsoi@cuhk.edu.hk

研究负责人电子邮件：

Study leader's E-mail：

 lijia_chen@cuhk.edu.hk

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：

香港九龍亞皆老街147K號香港眼科醫院3樓

研究负责人通讯地址：

香港九龍亞皆老街147K號香港眼科醫院4樓

Applicant address：

3/F, Hong Kong Eye Hospital, 147K Argyle Street, Kowloon, Hong Kong

Study leader's address：

4/F, Hong Kong Eye Hospital, 147K Argyle Street, Kowloon, Hong Kong

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：

香港中文大學眼科及視覺科學學系

Applicant's institution：

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong

研究负责人所在单位：

香港中文大學眼科及視覺科學學系

Affiliation of the Leader：

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong

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：

 KC/KE-22-0215/FR-4

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：

九龍中及九龍東聯網臨床研究倫理委員會

Name of the ethic committee：

Research Ethics Committee (Kowloon Central / Kowloon East)

伦理委员会批准日期：

Date of approved by ethic committee：

 2022-12-20 00:00:00

伦理委员会联系人：

Ms Lyon Chan

Contact Name of the ethic committee：

Ms Lyon Chan

伦理委员会联系地址：

香港九龍加士居道30號伊利沙伯醫院護士宿舍4樓414室

Contact Address of the ethic committee：

Room 414, Nurse Quarters, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong

伦理委员会联系人电话：

Contact phone of the ethic committee：

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：

醫務衞生局研究處

Primary sponsor：

Research Office, Health Bureau

研究实施负责（组长）单位地址：

香港上環林士街2號林士街多層停車場9樓

Primary sponsor's address：

9/F, Rumsey Street Multi-storey Carpark Building, 2 Rumsey Street, Sheung Wan, Hong Kong

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

香港

省(直辖市)：

市(区县)：

Country：

Hong Kong

Province：

City：

单位(医院)：

香港中文大學眼科及視覺科學學系

具体地址：

香港九龍亞皆老街147K號香港眼科醫院3樓

Institution
hospital：

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong

Address：

3/F, Hong Kong Eye Hospital, 147K Argyle Street, Kowloon, Hong Kong

经费或物资来源：

醫療衞生研究基金

Source(s) of funding：

Health and Medical Research Fund

研究疾病：

新生血管型老年黃斑病變、息肉狀脈絡膜血管病變  

Target disease：

Neovascular age-related macular degeneration, polypoidal choroidal vasculopathy

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：

 III期临床试验 

Study phase：

3

研究设计：

整群随机分组 

Study design：

Cluster randomization 

研究目的：

1. 比較Brolucizumab (Beovu)與Ranibizumab (Lucentis)及Aflibercept (Eylea)，評估對nAMD和PCV的療效和安全性。 2. 評估nAMD和PCV的多個基因變異，以及抗VEGF治療反應藥物基因關聯。 3. 建立和驗證分辨nAMD和PCV眼睛對抗VEGF治療反應的深度學習系統。 4. 以深度學習系統預測nAMD和PCV眼睛因抗VEGF注射所引起的視網膜血管炎/眼內炎症風險，以協助未來臨床管理。 5. 前瞻性地在醫院的真實環境中應用深度學習系統，評估其對分辨nAMD/PCV的眼睛對抗VEGF治療反應的表現。  

Objectives of Study：

1. To determine the efficacy and safety of Brolucizumab (Beovu), in comparison with Ranibizumab (Lucentis) and Aflibercept (Eylea), in treating nAMD and PCV in Hong Kong Chinese. 2. To determine the associations of multiple gene variants with nAMD and PCV, and the pharmacogenetic associations of these gene variants with the treatment responses of anti-VEGF. 3. To develop and validate a deep learning system for classifying eyes with nAMD/PCV into response or non-response with anti-VEGF treatment. 4. To further predict eyes with nAMD/PCV at risk of retinal vasculitis / intraocular inflammation due to intravitreal brolucizumab by the deep learning system to assist future clinical management. 5. To prospectively apply and evaluate the performance of the deep learning system for categorizing eyes with nAMD/PCV into response or non-response with anti-VEGF treatment in a hospital-based, real-world setting.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

隨機對照研究：
1) 年齡≥50歲；
2) 研究眼中有未經治療的活性 nAMD 或 PCV；
3) 最佳矯正視力 (BCVA) 在 Snellen 視力表上介於 20/200 和 20/40 之間；
4) 研究眼在 FA/ICGA 和 SDOCT 上有視網膜下液 (SRF) 和/或視網膜內液 (IRF) 滲漏；
5) 願意在香港中文大學眼科中心/香港中文大學醫院支付比公立醫院高的每次標準費用（HK$2,500）包括視力測試、眼壓測量和注射程序 ;
6) 願意遵循基於黃斑情況的治療策略（病況仍然活躍可能會導致更多但及時的注射）並隨機分配到不同的治療組進行 Beovu、Eylea 或 Lucentis 注射。

醫院現實研究：
未接受過 nAMD/PCV 抗 VEGF 治療的未治療眼（每種抗 VEGF 藥物 n=150）； 較願意在公立醫院繼續接受跟進，並根據臨床判斷和不同的等待時間接受其中一種抗VEGF藥物注射。

Inclusion criteria

Randomized-controlled study:
1) aged ≥50 years;
2) with untreated active nAMD or PCV in the study eye;
3) with a best-corrected visual acuity (BCVA) between 20/200 and 20/40 on Snellen chart;
4) the study eye has leakage on FA/ICGA and subretinal fluid (SRF) and/or intraretinal fluid (IRF) on SDOCT;
5) willing to pay a hospital fee per injection (HK$2,500) higher than public hospitals at the CUHK Eye Centre / CUHK Medical Centre, which is a standard charge for clinical services at both sites covering visual acuity test, intraocular pressure measurement and injection procedures;
6) willing to follow the treatment strategy based on macular conditions (this may incur more, but timely, injections if their condition is still active) and be randomized to different treatment arms for Beovu, Eylea or Lucentis injections.

Patients for the real-world, hospital-based study:
Treatment na?ve eyes with nAMD/PCV pending for anti-VEGF treatment (n=150 for each of the anti-VEGF agents); patients who prefer to continue their follow-up at the public hospitals over CUHK Eye Centre or CUHK Medical Centre and receive injections of one of the anti-VEGF agents per clinical judgment with variable waiting time to begin treatment.

排除标准：

1. 任何眼睛有任何活躍或曾出現眼內或眼周感染或炎症；
2. 研究眼睛曾接受除維生素補充劑外的nAMD/PCV治療；
3. 在研究登記時懷孕的女性患者（這不太可能，因為研究只包括年齡超過50歲的患者）。

Exclusion criteria：

1. Any active or previous intraocular or periocular infection or inflammation in either eye;
2. Previous treatment for nAMD/PCV other than vitamin supplements in the study eye;
3. Female patients who are pregnant at study enrolment (this is not likely as only patients aged >50 years will be included).

研究实施时间：

Study execute time：

从 From 2023-04-01 00:00:00至 To 2026-03-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-04-01 00:00:00 至 To 2026-03-31 00:00:00

干预措施：

Interventions：

组别：

nAMD - Beovu (RCT)

样本量：

 44

Group：

nAMD - Beovu (RCT)

Sample size：

干预措施：

3次Beovu負荷劑量注射，第12周起每4-6周BCVA和SDOCT檢查，按臨床需要繼續注射

干预措施代码：

Intervention：

3 Beovu loading doses, BCVA and SDOCT exam every 4-6 week starting from week 12, further injection as clinically needed

Intervention code：

组别：

nAMD - Eylea (RCT)

样本量：

 44

Group：

nAMD - Eylea (RCT)

Sample size：

干预措施：

3次Eylea負荷劑量注射，第12周起每4-6周BCVA和SDOCT檢查，按臨床需要繼續注射

干预措施代码：

Intervention：

3 Eylea loading doses, BCVA and SDOCT exam every 4-6 week starting from week 12, further injection as clinically needed

Intervention code：

组别：

nAMD - Lucentis (RCT)

样本量：

 44

Group：

nAMD - Lucentis (RCT)

Sample size：

干预措施：

3次Lucentis負荷劑量注射，第12周起每4-6周BCVA和SDOCT檢查，按臨床需要繼續注射

干预措施代码：

Intervention：

3 Lucentis loading doses, BCVA and SDOCT exam every 4-6 week starting from week 12, further injection as clinically needed

Intervention code：

组别：

PCV - Beovu (RCT)

样本量：

 44

Group：

PCV - Beovu (RCT)

Sample size：

干预措施：

3次Beovu負荷劑量注射，第12周起每4-6周BCVA和SDOCT檢查，按臨床需要繼續注射

干预措施代码：

Intervention：

3 Beovu loading doses, BCVA and SDOCT exam every 4-6 week starting from week 12, further injection as clinically needed

Intervention code：

组别：

PCV - Eylea (RCT)

样本量：

 44

Group：

PCV - Eylea (RCT)

Sample size：

干预措施：

3次Eylea負荷劑量注射，第12周起每4-6周BCVA和SDOCT檢查，按臨床需要繼續注射

干预措施代码：

Intervention：

3 Eylea loading doses, BCVA and SDOCT exam every 4-6 week starting from week 12, further injection as clinically needed

Intervention code：

组别：

PCV - Lucentis (RCT)

样本量：

 44

Group：

PCV - Lucentis (RCT)

Sample size：

干预措施：

3次Lucentis負荷劑量注射，第12周起每4-6周BCVA和SDOCT檢查，按臨床需要繼續注射

干预措施代码：

Intervention：

3 Lucentis loading doses, BCVA and SDOCT exam every 4-6 week starting from week 12, further injection as clinically needed

Intervention code：

组别：

nAMD-现实研究

样本量：

 300

Group：

nAMD-prospective, real-world study

Sample size：

干预措施：

按臨床指示進行3次Eylea或Lucentis負荷劑量注射, 第三針4-6周後進行BCVA和SDOCT檢查

干预措施代码：

Intervention：

3 loading doses of Eylea or Lucentis as clinically indicated every 1 month; BCVA and SDOCT exam 4-6 weeks after the third injection

Intervention code：

组别：

PCV-现实研究

样本量：

 300

Group：

PCV-prospective, real-world study

Sample size：

干预措施：

按臨床指示進行3次Eylea或Lucentis負荷劑量注射, 第三針4-6周後進行BCVA和SDOCT檢查

干预措施代码：

Intervention：

3 loading doses of Eylea or Lucentis as clinically indicated every 1 month; BCVA and SDOCT exam 4-6 weeks after the third injection

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 香港 

市(区县)：

  

Country：

China

Province：

Hong Kong

City：

单位(医院)：

 香港眼科醫院 

单位级别：

  

Institution
hospital：

Hong Kong Eye Hospital

Level of the institution：

国家：

 中国

省(直辖市)：

 香港 

市(区县)：

  

Country：

China

Province：

Hong Kong

City：

单位(医院)：

 威爾斯親王醫院 

单位级别：

  

Institution
hospital：

Prince of Wales Hospital

Level of the institution：

国家：

 中国

省(直辖市)：

 香港 

市(区县)：

  

Country：

China

Province：

Hong Kong

City：

单位(医院)：

 香港中文大學眼科中心 

单位级别：

  

Institution
hospital：

CUHK Eye Centre

Level of the institution：

国家：

 中国

省(直辖市)：

 香港 

市(区县)：

  

Country：

China

Province：

Hong Kong

City：

单位(医院)：

 香港中文大學醫院 

单位级别：

  

Institution
hospital：

CUHK Medical Centre

Level of the institution：

测量指标：

Outcomes：

指标中文名：

療效評估 (隨機對照研究)

指标类型：

主要指标

Outcome：

Efficacy assessment (RCT)

Type：

Primary indicator

测量时间点：

第12周

测量方法：

BCVA, SDOCT

Measure time point of outcome：

Week 12

Measure method：

BCVA, SDOCT

指标中文名：

nAMD和PCV單核苷酸多態性的藥理學關聯

指标类型：

主要指标

Outcome：

Pharmacogenetic associations of the SNPs with nAMD and PCV

Type：

Primary indicator

测量时间点：

测量方法：

DNA 提取、SNP 選擇和基因分型

Measure time point of outcome：

Measure method：

DNA extraction, SNP selection and genotyping

指标中文名：

深度學習模型

指标类型：

主要指标

Outcome：

Deep learning models

Type：

Primary indicator

测量时间点：

测量方法：

建立和驗證深度學習模型

Measure time point of outcome：

Measure method：

Establishment and validation of deep learning models

指标中文名：

療效評估 (隨機對照研究)

指标类型：

次要指标

Outcome：

Efficacy assessment (RCT)

Type：

Secondary indicator

测量时间点：

第52周

测量方法：

BCVA, SDOCT

Measure time point of outcome：

Week 52

Measure method：

BCVA, SDOCT

指标中文名：

療效評估 (現實研究)

指标类型：

次要指标

Outcome：

Efficacy assessment (real-world study)

Type：

Secondary indicator

测量时间点：

第3針後4-6周

测量方法：

BCVA, SDOCT

Measure time point of outcome：

4-6 weeks after third injection

Measure method：

BCVA, SDOCT

指标中文名：

nAMD和PCV單核苷酸多態性的基因關聯

指标类型：

次要指标

Outcome：

Genetic association of SNPs with nAMD and PCV

Type：

Secondary indicator

测量时间点：

测量方法：

DNA 提取、SNP 選擇和基因分型

Measure time point of outcome：

Measure method：

DNA extraction, SNP selection and genotyping

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

 使用后保存  

说明

保存10年

Fate of sample：

Preservation after use  

Note：

Preserved for 10 years

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 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）：

隨機對照研究中132名nAMD和132名PCV患者將以隨機化表以1:1:1 的比例隨機分配，分別接受 Beovu、Eylea 或 Lucentis，每個治療組有 44 名患者。執行 BCVA 測量、OCT和其他眼科檢查的研究人員將被遮盲，但患者和注射臨床醫生則為開放標籤。

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

The 132 nAMD and 132 PCV patients in RCT will be randomized 1:1:1 using a randomization table to receive Beovu, Eylea or Lucentis respectively, with 44 patients in each treatment arm. The investigators who perform BCVA measurement, OCT and other ocular investigations will be masked from the injected-drug, w

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：

執行 BCVA 測量、OCT和其他眼科檢查的研究人員將被遮盲，但患者和注射臨床醫生則為開放標籤。

Blinding：

The investigators who perform BCVA measurement, OCT and other ocular investigations will be masked from the injected-drug, which however, will be open-labelled to the patients and injecting clinicians.

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）：

N/A

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：

Patient data would be handled with utmost care taking care not to breach patient's privacy in any form. The data would be stored in secure cabinets and/or computers which would be password operated. To protect patient privacy, all research data would be handled in line with HA / Hospital’s policy in handling / storage / destruction of patients’ medical records. Electronic data would be saved in secured computer of the hospital with restricted access. USB Device would not be used for patient information nor personal data. Personal data (name, HKID, OPD / hospital numbers, address and any other personal identifiable information) would not be recorded on the project’s data sheets or electronic files. A study code would be used instead. The document of electronic file containing the linkage information between the study code and the identity of the patient would not contain any other information and would be kept separate from the study data files or data sheets with the same stringent security as the medical record. Any documents or electronic files containing personal identifiable information would be considered as part of the medical record and would be dealt with the same stringent regulations of security according to the hospital policies. All the investigators would be responsible for data handling and protection. All identifiable personal data will be anonymised and will follow the HA policy on handling of patient data privacy.

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

Patient data would be handled with utmost care taking care not to breach patient's privacy in any form. The data would be stored in secure cabinets and/or computers which would be password operated. To protect patient privacy, all research data would be handled in line with HA / Hospital’s policy in handling / storage / destruction of patients’ medical records. Electronic data would be saved in secured computer of the hospital with restricted access. USB Device would not be used for patient information nor personal data. Personal data (name, HKID, OPD / hospital numbers, address and any other personal identifiable information) would not be recorded on the project’s data sheets or electronic files. A study code would be used instead. The document of electronic file containing the linkage information between the study code and the identity of the patient would not contain any other information and would be kept separate from the study data files or data sheets with the same stringent security as the medical record. Any documents or electronic files containing personal identifiable information would be considered as part of the medical record and would be dealt with the same stringent regulations of security according to the hospital policies. All the investigators would be responsible for data handling and protection. All identifiable personal data will be anonymised and will follow the HA policy on handling of patient data privacy.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2023-03-27 11:34:05