Clinical trial NCT06743646: Efficacy and Safety of ZVS101e in Patients With Bietti 's Crystalline Dystrophy
Official title: A Multicenter, Randomized，Controlled，Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of ZVS101e Administered as a Single Subretinal Injection in Subjects With Bietti's Crystalline Dystrophy (BCD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Bietti Crystalline Corneoretinal Dystrophy
Bietti Crystalline Dystrophy
Keywords: gene replacement therapy
ZVS101e
AAV8-hCYP4V2
phase 3
Bietti crystalline corneoretinal dystrophy
Lead sponsor: Chigenovo Co., Ltd
Sponsor class: NETWORK
First posted: 2024-12-20
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, randomized and controlled phase 3 clinical trial.

Detailed description: Subjects who have signed the written informed consent form and who were eligible for enrollment after screening will be randomly assigned to the treatment group or untreated control group. Each Participant in the treatment group will receive a unilateral subretinal injection of ZVS101e in the study eye.

Participants in the control group will receive no treatment during the first 52 weeks of enrollment.

Eligibility criteria: Inclusion Criteria:

1. All of the following inclusion criteria should be met for enrollment into the trial:
2. Fully understand the purpose and requirements of this trial, voluntarily participate in the clinical trial and sign the informed consent form, and be able to complete all trial procedures as required by the protocol;
3. Clinical diagnosis of Bietti's crystalline dystrophy (BCD), age≥18 years ;
4. Genetic testing confirmed biallelic CYP4V2 mutations without other ophthalmic genetic diseases;
5. Best-corrected visual acuity of 5-60 ETDRS letters.

Exclusion Criteria:

1. The study eye has or has had macular lesions such as macular hole or macular neovascularization; glaucoma, diabetic retinopathy, or any other ocular disease that may preclude surgery or interfere with interpretation of the study endpoints
2. The study eye had received the following intraocular surgical treatments: retinal reattachment, vitrectomy;
3. The study eye had received any intraocular surgery, such as phacoemulsification 3 months prior to enrollment;
4. Previously treatment of either eye with gene therapy or stem cell therapy for BCD and other ocular diseases, including but not limited to viral vector gene therapy, RNA therapy;
5. Pregnant or lactating women;

Primary outcomes:
measure: Proportion of study eyes with a ≥15-letter improvement from baseline in BCVA
timeFrame: From baseline to Week 52
Secondary outcomes:
measure: Change from Baseline in BCVA
timeFrame: From baseline to Week 52
measure: Proportion of study eyes with a ≥10-letter improvement from baseline in BCVA
timeFrame: From baseline to Week 52
measure: Change from baseline in multi-luminance mobility test (MLMT) score
timeFrame: From baseline to Week 52
measure: Change from baseline in 25-Item visual function questionnaire (VFQ-25) score
timeFrame: From baseline to Week 52
measure: Change from Baseline in microperimetry
timeFrame: From baseline to Week 52
measure: Change from baseline in OCT
timeFrame: From baseline to Week 52
measure: Incidence and severity of ocular and systemic adverse events
timeFrame: From baseline to Week 52
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Guangzhou
country: China
facility: Zhongshan Ophthalmic Center, Sun Yat-sen University
state: Guangdong
city: Haerbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Eye Hospital
state: Tianjin
city: Wenzhou
country: China
facility: Eye Hospital, Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Chigenovo Co., Ltd
name: Jinlu Zhang, MD
role: STUDY_DIRECTOR
References:
citation: Jia R, Meng X, Chen S, Zhang F, Du J, Liu X, Yang L. AAV-mediated gene-replacement therapy restores viability of BCD patient iPSC derived RPE cells and vision of Cyp4v3 knockout mice. Hum Mol Genet. 2023 Jan 1;32(1):122-138. doi: 10.1093/hmg/ddac181.
citation: Wang J, Zhang J, Yu S, Li H, Chen S, Luo J, Wang H, Guan Y, Zhang H, Yin S, Wang H, Li H, Liu J, Zhu J, Yang Q, Sha Y, Zhang C, Yang Y, Yang X, Zhang X, Zhao X, Wang L, Yang L, Wei W. Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial. Signal Transduct Target Ther. 2024 Apr 24;9(1):95. doi: 10.1038/s41392-024-01806-3.