Back to resultsCRISPR/Cas13-mediated RNA Targeting Therapy for the Treatment of nAMD Investigator-Initiated Trial (SIGHT-I)
Primary Purpose
Neovascular Age-related Macular Degeneration(nAMD)
Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
HG202
Sponsored by
About this trial
This is an interventional treatment trial for Neovascular Age-related Macular Degeneration(nAMD) focused on measuring Macular Degeneration/nAMD/wAMD/Gene-editing/CRISPR/HG202
Eligibility Criteria
Inclusion Criteria: Males or females ≥ 50 and ≤ 80 years at the time of signing the ICF Diagnosed of choroidal neovascularization (CNV) secondary to AMD in the study eye; Best-corrected visual acuity (BCVA) ranged from 73 to 23 early treatment diabetic retinopathy study (ETDRS)letter score (corresponding to 20/32 to 20/320 of Snellen visual acuity) in the study eye; BCVA in the non-study eye had an ETDRS letter score of 19(equivalent to Snellen visual acuity20/400) and above; Able to perform visual acuity and retinal function tests and able and willing to comply with study procedures for this clinical trial; RESPONSIVE SUBJECTS: History of need for and responsive to anti-VEGF therapy in the study eye NON-RESPONSIVE SUBJECTS: History of receiving anti-VEGF therapy but is resistant to treatment, which is defined as: a. complete or near-complete remission of subretinal fluid after the initial 3 doses of anti-VEGF agents and thenno improvement (less than 50um reduction) or deterioration of CRT by OCT Exclusion Criteria: Subretinal hemorrhage, scarring, or fibrosis of greater than 50% of the total lesion in the study eye; Any condition in the Investigator's opinion that could limit visual improvement in the study eye; Other ocular diseases that may affect central vision in the study eye (e.g., retinal vein occlusion, retinal detachment, macular hole, optic nerve disease, etc.); Presence of CNV not due to nAMD in the study eye, Uncontrolled glaucoma in the study eye; Active intraocular inflammation or a history of uveitis in either eye; History or presence of corneal dystrophy in the study eye; Subjects with immunodeficiency diseases prone to opportunistic infections; History of other intraocular surgery in the study eye within 3 months prior to baseline that in the Investigator's opinion could impact healing or study outcome interpretation; Prior gene therapy or oligonucleotide therapy; History of acute coronary syndrome, myocardial infarction, coronary revascularization, cerebrovascular accident, or transient ischemic attack within 6 months prior to the Screening Visit; Other conditions judged by the investigator as inappropriate for the study.
Sites / Locations
- Eye & ENT Hospital of Fudan UniversityRecruiting
- Tianjin Medical University Eye HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
HG202
Arm Description
Outcomes
Primary Outcome Measures
Incidence and severity of ocular and systemic adverse events
Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Secondary Outcome Measures
Incidence and severity of ocular and systemic adverse events
Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Change from baseline in best-corrected visual acuity (BCVA)
Change from baseline in BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart in the study eye at different doses
Change from baseline in central retinal thickness (CRT)
Change from baseline in central retinal thickness (CRT) as measured by optical coherence tomography (OCT) in the study eye at different doses
Change From baseline in annualized rate of supplemental injections
Change from baseline in the number of anti-VEGF injections which is annualized to a per year rate in the study eye at different doses
Full Information
NCT ID
NCT06031727
First Posted
September 1, 2023
Last Updated
September 18, 2023
Sponsor
HuidaGene Therapeutics Co., Ltd.
Collaborators
Tianjin Medical University Eye Hospital, Eye & ENT Hospital of Fudan University
1. Study Identification
Unique Protocol Identification Number
NCT06031727
Brief Title
CRISPR/Cas13-mediated RNA Targeting Therapy for the Treatment of nAMD Investigator-Initiated Trial (SIGHT-I)
Official Title
A Trial to Evaluate the Safety, Tolerability, and Efficacy of CRISPR-Cas13 RNA-editing Therapy Targeting Knockdown of Vascular Endothelial Growth Factor A (HG202) in the Treatment of Neovascular Age-related Macular Degeneration (nAMD)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 4, 2023 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
June 27, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HuidaGene Therapeutics Co., Ltd.
Collaborators
Tianjin Medical University Eye Hospital, Eye & ENT Hospital of Fudan University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Age-related macular degeneration (AMD) is a progressive disease leading to severe and irreversible vision loss of which the neovascular AMD (nAMD) accounted for 90% blindness in AMD. nAMD is primarily driven by the perturbation of vascular endothelial growth factor (VEGF). VEGF overexpression leads to abnormal growth of choroidal neovascularization (CNV), which is a hallmark of AMD. Although anti-VEGF agents are effective in treating nAMD, long-term efficacy decreases over time due to the need for repeated injections impacting patient compliance with treatment regimen while patients still may lose vision during the 7th or 8th year of treatment. These frequent intravitreal injections can increase the risk of complications, including submacular hemorrhage, intraocular hypertension, inflammation, and retinal detachment. Furthermore, there are up to 46% of nAMD patients using anti-VEGF agents who have shown poor response or have developed tachyphylaxis with anti-VEGF therapies. HG202 is a CRISPR/Cas13 RNA-editing therapy packaging novel high-fidelity Cas13 technology using one single AAV vector to partially knock-down the expression of VEGFA and thus inhibit CNV formation in AMD patients who are either responsive or non-responsive to anti-VEGF agents. The long-term, stable delivery of HG202 following a one (1) time gene-editing therapy treatment for nAMD could potentially reduce the frequent injection treatment burden of currently available therapies AND treat nAMD patients who are non-responsive to anti-VEGF therapies and have no treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neovascular Age-related Macular Degeneration(nAMD)
Keywords
Macular Degeneration/nAMD/wAMD/Gene-editing/CRISPR/HG202
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HG202
Arm Type
Experimental
Intervention Type
Genetic
Intervention Name(s)
HG202
Intervention Description
Method of Administration: Once unilateral subretinal injection; The duration of the study is about 52 weeks for each subject including a 4 weeks screening period, enrollment/baseline visit, treatment visit and 48 weeks follow-up period.
Primary Outcome Measure Information:
Title
Incidence and severity of ocular and systemic adverse events
Description
Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Incidence and severity of ocular and systemic adverse events
Description
Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Time Frame
48 weeks
Title
Change from baseline in best-corrected visual acuity (BCVA)
Description
Change from baseline in BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart in the study eye at different doses
Time Frame
24 and 48 weeks
Title
Change from baseline in central retinal thickness (CRT)
Description
Change from baseline in central retinal thickness (CRT) as measured by optical coherence tomography (OCT) in the study eye at different doses
Time Frame
24 and 48 weeks
Title
Change From baseline in annualized rate of supplemental injections
Description
Change from baseline in the number of anti-VEGF injections which is annualized to a per year rate in the study eye at different doses
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or females ≥ 50 and ≤ 80 years at the time of signing the ICF
Diagnosed of choroidal neovascularization (CNV) secondary to AMD in the study eye;
Best-corrected visual acuity (BCVA) ranged from 73 to 23 early treatment diabetic retinopathy study (ETDRS)letter score (corresponding to 20/32 to 20/320 of Snellen visual acuity) in the study eye;
BCVA in the non-study eye had an ETDRS letter score of 19(equivalent to Snellen visual acuity20/400) and above;
Able to perform visual acuity and retinal function tests and able and willing to comply with study procedures for this clinical trial;
RESPONSIVE SUBJECTS:
History of need for and responsive to anti-VEGF therapy in the study eye
NON-RESPONSIVE SUBJECTS:
History of receiving anti-VEGF therapy but is resistant to treatment, which is defined as: a. complete or near-complete remission of subretinal fluid after the initial 3 doses of anti-VEGF agents and thenno improvement (less than 50um reduction) or deterioration of CRT by OCT
Exclusion Criteria:
Subretinal hemorrhage, scarring, or fibrosis of greater than 50% of the total lesion in the study eye;
Any condition in the Investigator's opinion that could limit visual improvement in the study eye;
Other ocular diseases that may affect central vision in the study eye (e.g., retinal vein occlusion, retinal detachment, macular hole, optic nerve disease, etc.);
Presence of CNV not due to nAMD in the study eye,
Uncontrolled glaucoma in the study eye;
Active intraocular inflammation or a history of uveitis in either eye;
History or presence of corneal dystrophy in the study eye;
Subjects with immunodeficiency diseases prone to opportunistic infections;
History of other intraocular surgery in the study eye within 3 months prior to baseline that in the Investigator's opinion could impact healing or study outcome interpretation;
Prior gene therapy or oligonucleotide therapy;
History of acute coronary syndrome, myocardial infarction, coronary revascularization, cerebrovascular accident, or transient ischemic attack within 6 months prior to the Screening Visit;
Other conditions judged by the investigator as inappropriate for the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Director
Phone
+86 021-25076143
Email
HG20201@huidagene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Huidagene Therapeuticd Co., Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Eye & ENT Hospital of Fudan University
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gezhi Xu, PhD
Phone
+86 18017316316
Email
drxugezhi@163.com
Facility Name
Tianjin Medical University Eye Hospital
City
Tianjin
State/Province
Tianjing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaorong Li, PhD
Phone
+86 18622818042
Email
Xiaorli@163.com
12. IPD Sharing Statement
Learn more about this trial
CRISPR/Cas13-mediated RNA Targeting Therapy for the Treatment of nAMD Investigator-Initiated Trial (SIGHT-I)
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