xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06031727</url>
    </required_header>
    <id_info>
      <org_study_id>HG20201</org_study_id>
      <nct_id>NCT06031727</nct_id>
    </id_info>
    <brief_title>CRISPR/Cas13-mediated RNA Targeting Therapy for the Treatment of nAMD Investigator-Initiated Trial (SIGHT-I)</brief_title>
    <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)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>HuidaGene Therapeutics Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Tianjin Medical University Eye Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Eye &amp; ENT Hospital of Fudan University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>HuidaGene Therapeutics Co., Ltd.</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Age-related macular degeneration (AMD) is a progressive disease leading to severe and&#xD;
        irreversible vision loss of which the neovascular AMD (nAMD) accounted for 90% blindness in&#xD;
        AMD. nAMD is primarily driven by the perturbation of vascular endothelial growth factor&#xD;
        (VEGF). VEGF overexpression leads to abnormal growth of choroidal neovascularization (CNV),&#xD;
        which is a hallmark of AMD. Although anti-VEGF agents are effective in treating nAMD,&#xD;
        long-term efficacy decreases over time due to the need for repeated injections impacting&#xD;
        patient compliance with treatment regimen while patients still may lose vision during the 7th&#xD;
        or 8th year of treatment. These frequent intravitreal injections can increase the risk of&#xD;
        complications, including submacular hemorrhage, intraocular hypertension, inflammation, and&#xD;
        retinal detachment. Furthermore, there are up to 46% of nAMD patients using anti-VEGF agents&#xD;
        who have shown poor response or have developed tachyphylaxis with anti-VEGF therapies. HG202&#xD;
        is a CRISPR/Cas13 RNA-editing therapy packaging novel high-fidelity Cas13 technology using&#xD;
        one single AAV vector to partially knock-down the expression of VEGFA and thus inhibit CNV&#xD;
        formation in AMD patients who are either responsive or non-responsive to anti-VEGF agents.&#xD;
        The long-term, stable delivery of HG202 following a one (1) time gene-editing therapy&#xD;
        treatment for nAMD could potentially reduce the frequent injection treatment burden of&#xD;
        currently available therapies AND treat nAMD patients who are non-responsive to anti-VEGF&#xD;
        therapies and have no treatment.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 30, 2023</start_date>
    <completion_date type="Anticipated">June 27, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <phase>Early Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence and severity of ocular and systemic adverse events</measure>
      <time_frame>24 weeks</time_frame>
      <description>Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Incidence and severity of ocular and systemic adverse events</measure>
      <time_frame>48 weeks</time_frame>
      <description>Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in best-corrected visual acuity (BCVA)</measure>
      <time_frame>24 and 48 weeks</time_frame>
      <description>Change from baseline in BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart in the study eye at different doses</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in central retinal thickness (CRT)</measure>
      <time_frame>24 and 48 weeks</time_frame>
      <description>Change from baseline in central retinal thickness (CRT) as measured by optical coherence tomography (OCT) in the study eye at different doses</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change From baseline in annualized rate of supplemental injections</measure>
      <time_frame>48 weeks</time_frame>
      <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</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">12</enrollment>
    <condition>Neovascular Age-related Macular Degeneration(nAMD)</condition>
    <arm_group>
      <arm_group_label>HG202</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Genetic</intervention_type>
      <intervention_name>HG202</intervention_name>
      <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.</description>
      <arm_group_label>HG202</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Males or females ≥ 50 and ≤ 80 years at the time of signing the ICF&#xD;
  &#xD;
            -  Diagnosed of choroidal neovascularization (CNV) secondary to AMD in the study eye;&#xD;
  &#xD;
            -  Best-corrected visual acuity (BCVA) ranged from 73 to 23 early treatment diabetic&#xD;
               retinopathy study (ETDRS)letter score (corresponding to 20/32 to 20/320 of Snellen&#xD;
               visual acuity) in the study eye;&#xD;
  &#xD;
            -  BCVA in the non-study eye had an ETDRS letter score of 19(equivalent to Snellen visual&#xD;
               acuity20/400) and above;&#xD;
  &#xD;
            -  Able to perform visual acuity and retinal function tests and able and willing to&#xD;
               comply with study procedures for this clinical trial;&#xD;
  &#xD;
          RESPONSIVE SUBJECTS:&#xD;
  &#xD;
            -  History of need for and responsive to anti-VEGF therapy in the study eye&#xD;
  &#xD;
          NON-RESPONSIVE SUBJECTS:&#xD;
  &#xD;
            -  History of receiving anti-VEGF therapy but is resistant to treatment, which is defined&#xD;
               as: a. complete or near-complete remission of subretinal fluid after the initial 3&#xD;
               doses of anti-VEGF agents and thenno improvement (less than 50um reduction) or&#xD;
               deterioration of CRT by OCT&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Subretinal hemorrhage, scarring, or fibrosis of greater than 50% of the total lesion&#xD;
               in the study eye;&#xD;
  &#xD;
            -  Any condition in the Investigator's opinion that could limit visual improvement in the&#xD;
               study eye;&#xD;
  &#xD;
            -  Other ocular diseases that may affect central vision in the study eye (e.g., retinal&#xD;
               vein occlusion, retinal detachment, macular hole, optic nerve disease, etc.);&#xD;
  &#xD;
            -  Presence of CNV not due to nAMD in the study eye,&#xD;
  &#xD;
            -  Uncontrolled glaucoma in the study eye;&#xD;
  &#xD;
            -  Active intraocular inflammation or a history of uveitis in either eye;&#xD;
  &#xD;
            -  History or presence of corneal dystrophy in the study eye;&#xD;
  &#xD;
            -  Subjects with immunodeficiency diseases prone to opportunistic infections;&#xD;
  &#xD;
            -  History of other intraocular surgery in the study eye within 3 months prior to&#xD;
               baseline that in the Investigator's opinion could impact healing or study outcome&#xD;
               interpretation;&#xD;
  &#xD;
            -  Prior gene therapy or oligonucleotide therapy;&#xD;
  &#xD;
            -  History of acute coronary syndrome, myocardial infarction, coronary revascularization,&#xD;
               cerebrovascular accident, or transient ischemic attack within 6 months prior to the&#xD;
               Screening Visit;&#xD;
  &#xD;
            -  Other conditions judged by the investigator as inappropriate for the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>50 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Study Director</last_name>
      <role>Study Director</role>
      <affiliation>Huidagene Therapeuticd Co., Ltd.</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Study Director</last_name>
      <phone>+86 021-25076143</phone>
      <email>HG20201@huidagene.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Eye &amp; ENT Hospital of Fudan University</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Gezhi Xu, PhD</last_name>
        <phone>+86 18017316316</phone>
        <email>drxugezhi@163.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Tianjin Medical University Eye Hospital</name>
        <address>
          <city>Tianjin</city>
          <state>Tianjing</state>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Xiaorong Li, PhD</last_name>
        <phone>+86 18622818042</phone>
        <email>Xiaorli@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 1, 2023</study_first_submitted>
    <study_first_submitted_qc>September 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 4, 2023</last_update_submitted>
    <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Macular Degeneration/nAMD/wAMD/Gene-editing/CRISPR/HG202</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Macular Degeneration</mesh_term>
      <mesh_term>Wet Macular Degeneration</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06031727
  org study id: HG20201
  nct id: NCT06031727
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence and severity of ocular and systemic adverse events
  time frame: 24 weeks
  description: Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
  measure: Incidence and severity of ocular and systemic adverse events
  time frame: 48 weeks
  description: Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
  measure: Change from baseline in best-corrected visual acuity (BCVA)
  time frame: 24 and 48 weeks
  description: Change from baseline in BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) chart in the study eye at different doses
  measure: Change from baseline in central retinal thickness (CRT)
  time frame: 24 and 48 weeks
  description: Change from baseline in central retinal thickness (CRT) as measured by optical coherence tomography (OCT) in the study eye at different doses
  measure: Change From baseline in annualized rate of supplemental injections
  time frame: 48 weeks
  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
  arm group label: HG202
  arm group type: Experimental
  intervention type: Genetic
  intervention name: HG202
  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.
  arm group label: HG202
  criteria: 
  gender: All
  minimum age: 50 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Study Director
  role: Study Director
  affiliation: Huidagene Therapeuticd Co., Ltd.
  last name: Study Director
  phone: +86 021-25076143
  email: HG20201@huidagene.com
  facility: 
  contact: 
  facility: 
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Macular Degeneration
  mesh term: Wet Macular Degeneration