A Study of EXG102-031 in Participants With wAMD

An Open-label, Dose-escalation Phase I/IIa Study to Evaluate the Safety and Efficacy of EXG102-031 Intraocular Injection in Participants With Neovascular Age-related Macular Degeneration（wAMD）

In neovascular (wet) age-related macular degeneration (wAMD), the macula, or the part of the eye that provides the clear, detailed central vision, is being affected by abnormal blood vessel growth and leakage. This leakage affects the vision over time and can lead to severe blurriness or blinding. EXG102-031 was made to block the extra vessel formation which would lead to less leakage affecting the vision. Before EXG102-031 can be tested for its efficacy (if it makes vision better), it must be tested to see if it is safely tolerated to confirm it can continue to be studied in more patients with wAMD.

Study Overview

• Status: Recruiting
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Biological: EXG102-031

Detailed Description

Age-related macular degeneration (AMD) is a major cause of blindness and visual impairment in older adults. The wet form of AMD, also called neovascular AMD (nAMD) usually causes faster vision loss than the dry form. The most common current treatments of nAMD are products that inhibit vascular endothelial growth factor (VEGF) (including ranibizumab (LUCENTIS®, Genentech) and aflibercept (EYLEA®, Regeneron) and are delivered by intravitreal injections at 4 to 16 week intervals and continued indefinitely. This Open-label, Dose-escalation Phase I/IIa Study is designed to evaluate the safety and efficacy of EXG102-031 intraocular Injection in participants with wet(Neovascular) Age-related Macular Degeneration（wAMD）.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sara Yang; Phone Number: +86 13957164092; Email: sarayang@exegenesisbio.com

Study Locations

• China
  • Beijing
    • Peking, Beijing, China, 100000
      • Not yet recruiting
      • Beijing Hospital
      • Contact: Haijuan Zhao
      • Principal Investigator: Xiaobing Yu, PhD
    • Peking, Beijing, China, 100000
      • Not yet recruiting
      • Beijing Tongren Hospital,CMU
      • Contact: Yuyang Dai
      • Principal Investigator: Wenbin Wei, PhD
      • Principal Investigator: Haicheng She, PhD
    • Peking, Beijing, China, 100000
      • Recruiting
      • Peking University People's Hospital
      • Contact: Lijue Wang
      • Principal Investigator: Mingwei Zhao, PhD
  • Chongqing
    • Chongqing, Chongqing, China
      • Not yet recruiting
      • The Southwest Hospital of Amu
      • Contact: Linli Xie
      • Principal Investigator: Yong Liu, PhD
  • Hubei
    • Wuhai, Hubei, China
      • Recruiting
      • Central theater General Hospital
      • Contact: Airong Yu
      • Principal Investigator: Yanping Song, PhD
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Not yet recruiting
      • Jiangsu Provinve Hospital
      • Contact: Yi Chai
      • Principal Investigator: Qinghuai Liu, PhD
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • The Second Affiliated Hospital Zhejiang University School of Medicine
      • Contact: Zourong Ruan
      • Principal Investigator: Ke Yao, PhD
    • Wenzhou, Zhejiang, China
      • Not yet recruiting
      • Eye Hospital,WMU
      • Contact: Zhishu Bao
      • Principal Investigator: Jia Qu, PhD
      • Principal Investigator: Xiaoling Liu, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, age ≥ 50 years of age;
2. Diagnosis of wAMD and current active lesion in the study eye at Screening;
3. An ETDRS BCVA letter scores between 73 and 9 letters in the study eye;
4. Response to anti-VEGF treatment within 6 months prior to screening or at the time of screening introduction;
5. The study eye must be a Intraocular lens eye(post-cataract surgery status) and be at least 1 month post IOL implantation at enrollment;
6. Voluntarily agree to participate in the clinical trial, understand the trial procedures, and be capable of signing the informed consent form before screening.

Exclusion Criteria:

1. Presence of any ocular disease or history of disease in the study eye other than wAMD that may affect central visual acuity and/or macular detection;
2. Presence in the study eye of CNV or macular pathology pathography due to causes other than wAMD;
3. The study eye has severe and irreversible retinal structural damage involving the fovea (such as retinal pigment epithelial (RPE) atrophy, retinal fibrosis, laser scars, dense hard exudation); Or other retinal damage in the target eye that, in the opinion of the investigator, may impede visual improvement after resolution of macular edema ;
4. Subretinal hemorrhage accumulating the central fovea of the study eye, with an area of hemorrhage ≥ 4 optic disc diameters;
5. Presence of advanced glaucoma or uncontrolled ocular hypertension in the study eye;
6. Prior receipt of any ocular or systemic gene therapy agent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation-Cohort 1; Genetic : EXG102-031	Biological: EXG102-031; EXG102-031 is a recombinant adeno-associated virus (rAAV) expressing an angiopoietin domain and VEGF receptor (ABD-VEGFR) fusion protein. EXG102-031 will be administered by subretinal injection.
Experimental: Dose escalation-Cohort 2; Genetic : EXG102-031	Biological: EXG102-031; EXG102-031 is a recombinant adeno-associated virus (rAAV) expressing an angiopoietin domain and VEGF receptor (ABD-VEGFR) fusion protein. EXG102-031 will be administered by subretinal injection.
Experimental: Dose escalation-Cohort 3; Genetic : EXG102-031	Biological: EXG102-031; EXG102-031 is a recombinant adeno-associated virus (rAAV) expressing an angiopoietin domain and VEGF receptor (ABD-VEGFR) fusion protein. EXG102-031 will be administered by subretinal injection.
Experimental: Dose escalation-Cohort 4; Genetic : EXG102-031	Biological: EXG102-031; EXG102-031 is a recombinant adeno-associated virus (rAAV) expressing an angiopoietin domain and VEGF receptor (ABD-VEGFR) fusion protein. EXG102-031 will be administered by subretinal injection.
Experimental: Dose escalation-Cohort 5; Genetic : EXG102-031	Biological: EXG102-031; EXG102-031 is a recombinant adeno-associated virus (rAAV) expressing an angiopoietin domain and VEGF receptor (ABD-VEGFR) fusion protein. EXG102-031 will be administered by subretinal injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events)	incidence of ocular and non-ocular AEs and SAEs	24 weeks following EXG102-031 administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (Participants With Ocular and Non-ocular AEs (Adverse Events) and SAEs (Serious Adverse Events)	incidence of ocular and non-ocular AEs and SAEs	52 weeks following EXG102-031 administration
Change From Baseline in BCVA (Best Corrected Visual Acuity)	Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision.	52 weeks following EXG102-031 administration
Change From Baseline in CRT (Central Retinal Thickness)	Retinal fluid status of the study eye was evaluated using spectral domain OCT (Optical Coherence Tomography). A decrease in value indicates a decrease in fluid	52 weeks following EXG102-031 administration
Supplemental Injections (Annualized Rate of Supplemental Injections)	The number of supplemental anti-VEGF injections given after EXG102-031 was administered.	52 weeks following EXG102-031 administration

Collaborators and Investigators

• Sponsor: Hangzhou Jiayin Biotech Ltd
• Investigators: Principal Investigator: Mingwei ZHAO, PhD, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 4, 2023
• First Submitted That Met QC Criteria: December 13, 2023
• First Posted (Actual): December 28, 2023

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 6, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Wet Age-related Macular Degeneration
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: EXG102-031-111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No