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CRISPR/cas13-medIated RNA tarGeting tHerapy for the Treatment of Neovascular Age-related Macular Degeneration Investigator-initiated Trial (SIGHT-I)

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ClinicalTrials.gov Identifier: NCT06031727
Recruitment Status : Recruiting
First Posted : September 11, 2023
Last Update Posted : November 13, 2023
Sponsor:
Collaborators:
Tianjin Medical University Eye Hospital
Eye & ENT Hospital of Fudan University
Information provided by (Responsible Party):
HuidaGene Therapeutics Co., Ltd.

Tracking Information
First Submitted Date  ICMJE September 1, 2023
First Posted Date  ICMJE September 11, 2023
Last Update Posted Date November 13, 2023
Actual Study Start Date  ICMJE September 4, 2023
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 4, 2023)
Incidence and severity of ocular and systemic adverse events [ Time Frame: 24 weeks ]
Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2023)
  • Incidence and severity of ocular and systemic adverse events [ Time Frame: 48 weeks ]
    Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
  • Change from baseline in best-corrected visual acuity (BCVA) [ Time Frame: 24 and 48 weeks ]
    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) [ Time Frame: 24 and 48 weeks ]
    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 [ Time Frame: 48 weeks ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CRISPR/cas13-medIated RNA tarGeting tHerapy for the Treatment of Neovascular Age-related Macular Degeneration Investigator-initiated Trial (SIGHT-I)
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neovascular Age-related Macular Degeneration(nAMD)
Intervention  ICMJE Genetic: HG202
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.
Study Arms  ICMJE Experimental: HG202
Intervention: Genetic: HG202
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 4, 2023)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 27, 2025
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Director +86 021-25076143 HG20201@huidagene.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT06031727
Other Study ID Numbers  ICMJE HG20201
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party HuidaGene Therapeutics Co., Ltd.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE HuidaGene Therapeutics Co., Ltd.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Tianjin Medical University Eye Hospital
  • Eye & ENT Hospital of Fudan University
Investigators  ICMJE
Study Director: Study Director Huidagene Therapeuticd Co., Ltd.
PRS Account HuidaGene Therapeutics Co., Ltd.
Verification Date November 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP