Safety and Efficacy Study of NGGT001 in Bietti Crystalline Corneoretinal Dystrophy Subjects

A Phase I/II Study for Subretinal Injection of NGGT001 in Patients With Bietti Crystalline Corneoretinal Dystrophy

The objective of this study is to evaluate the safety, tolerability, and efficacy of subretinal injection of NGGT001 in patients with Bietti Crystalline Corneoretinal Dystrophy (BCD) and to recommend the optimal dosage for future clinical administration.

Study Overview

• Status: Active, not recruiting
• Conditions: Bietti Crystalline Corneoretinal Dystrophy
• Intervention / Treatment: Biological: NGGT001

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University)
  • Fujian
    • Xiamen, Fujian, China, 361000
      • Xiamen Eye Center of Xiamen University

Participation Criteria

Eligibility Criteria

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

Description

1. Age ≥ 18 years old.
2. Male or female.
3. Confirmed diagnosis of BCD.
4. Molecular diagnosis confirmed cytochrome P450 family 4 subfamily v member 2 (CYP4V2) mutation.
5. AAV2 neutralizing antibody titer ≤1:5120.
6. 0.05 ≤ Best Corrected Visual Acuity (BCVA) ≤ 0.3.
7. -6.00D ≤ Refractive error ≤ +3.00D.
8. Agree to take contraceptive measures from the start of the study until one year after medication administration.
9. Volunteer to participate in the study and sign informed consent.

Exclusion Criteria:

1. There are choroidal neovascularization or other ocular diseases caused by BCD, which are considered to affect the operation or interfere with the interpretation of clinical endpoint.
2. Patients with evidence of neovascularization or suspected neovascularization, and the presence of tubular reflectivity in the neuroepithelial layer as shown by OCT.
3. Those who had used any of the treatment drugs within 6 months before enrollment, such as Lucentis, Avastin, Conbercept, Triamcinolone acetonide, etc. These may affect the experimental observation.
4. The treated eyes have undergone intraocular surgery, such as photodynamic therapy (PDT), vitrectomy, periocular vascular bypass surgery, etc., or need intraocular surgery in the process of clinical research, such as cataract surgery, retinal laser therapy, etc.
5. Have used or may use systemic drugs that may cause eye damage, such as psoralen, tamoxifen, etc.
6. Highly sensitive or allergic to ingredients in the test drug (with allergic history of two or more drugs or food).
7. Physical examination, vital signs, and laboratory examination (such as blood routine, urine routine, blood biochemistry, coagulation function, immunology examination, etc.) are abnormal and clinically significant, or the investigators believe that the abnormal indicators have clinical significance.
8. There are diseases or medical histories that may affect drug safety or in vivo processes, especially cardiovascular, liver, kidney, endocrine, digestive tract, lung, nerve, blood, tumor, immune or metabolic disorders considered by investigators to be of clinical significance.
9. Participated in clinical trials of other drugs or medical devices within three months before enrollment.
10. Female patients who are pregnant or lactating.
11. Any other conditions which lead the investigator to determine the participant is unsuitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NGGT001; Single Arm: This study is a single-arm design in which all participants receive the NGGT001 gene therapy administered via subretinal injection. Participants are divided into three dose-escalation groups to evaluate safety and efficacy.	Biological: NGGT001; Using a recombinant adeno-associated virus (AAV) vector to deliver the gene CYP4V2 via subretinal injection for the treatment of crystalline retinal degeneration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs) from baseline to 52 weeks.	To evaluate the incidence and severity of AEs, including serious AEs (SAEs) of subretinal injection of NGGT001 in patients with BCD.	52 weeks
Evaluate the improvement in BCVA compared to baseline at Week 12, 26 and 52.	To evaluate the BCVA in ETDRS test of subretinal injection of NGGT001 from baseline to W12, 26 and 52.	Week 12, Week 26 and Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of microperimetry changes in dB compared to baseline at Week 12, 26 and 52.	Retinal sensitivity will be assessed using the MP-3 Type Microperimeter. This will be measured in dB (decibels), and the retinal sensitivity analysis will be conducted based on these readings.	Week 12, Week 26 and Week 52
Assessment of contrast sensitivity (CS) changes in dB compared to baseline at Week 12, 26 and 52.	Changes in contrast sensitivity (CS) will be evaluated, and the measurements will be analyzed in decibels (dB).	Week 12, Week 26 and Week 52
Assessment of Optical Coherence Tomography (OCT) retinal thickness changes compared to baseline at Week 12, 26 and 52.	Retinal thickness will be measured using Optical Coherence Tomography (OCT), and the outcome will be expressed in micrometers (µm).	Week 12, Week 26 and Week 52
Assessment of Multi-Luminance Mobility Test (MLMT) score changes compared to baseline at Week 12, 26 and 52.	Multi-Luminance Mobility Test (MLMT) will assess subjects' daily life quality across different lighting conditions. The results will be categorized by the different light intensity levels, and the aggregate scores will be used to assess mobility performance	Week 12, Week 26 and Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Static Visual Fields (SVF) changes compared to baseline at Week 12, 26 and 52.	Static Visual Fields (SVF): Changes in visual field sensitivity will be evaluated at Weeks 12, 26 and 52, compared to baseline. The measurements will be expressed in light sensitivity units (dB).	Week 12, Week 26 and Week 52
Assessment of Fundus Autofluorescence (FAF) retinal structural changes compared to baseline at Week 12, 26 and 52.	Retinal structural changes will be assessed at Week 12 and 26, compared to baseline. Fundus Autofluorescence (FAF) imaging will be used to evaluate the intensity of autofluorescence, and changes will be assessed using a dB threshold to measure variations over time in comparison to baseline.	Week 12, Week 26 and Week 52
Assessment of Quality of Life Questionnaire score changes compared to baseline at Week 12, 26 and 52.	Quality of Life Questionnaire score will be measured at Week 12, 26 and 52, compared to baseline.	Week 12, Week 26 and Week 52
Assessment of MNRead Test changes compared to baseline at Week 12, 26 and 52.	MNRead Test results will be evaluated at Week 12, 26 and 52, compared to baseline, assessing vision function.	Week 12, Week 26 and Week 52

Collaborators and Investigators

• Sponsor: NGGT (Suzhou) Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2024
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): September 26, 2029

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Actual): November 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: BCD; Bietti Crystalline Corneoretinal Dystrophy
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Corneal Diseases; Eye Diseases, Hereditary; Retinal Diseases; Corneal Dystrophies, Hereditary
• Other Study ID Numbers: NGGT001-P-2301

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