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/NCT06022744</url>
    </required_header>
    <id_info>
      <org_study_id>SHGH-LX109</org_study_id>
      <nct_id>NCT06022744</nct_id>
    </id_info>
    <brief_title>An Exploratory Clinical Trial Evaluating LX109 Gene Therapy in Patients With nAMD</brief_title>
    <official_title>An Exploratory Clinical Trial Evaluating LX109 Gene Therapy in Patients With Neovascular Age-related Macular Degeneration (nAMD)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        To evaluate the safety and tolerability of intravitreal injection of LX109 in patients with&#xD;
        nAMD.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In this study, 9 to 12 participants were enrolled in an open monocular, single dose&#xD;
        escalation study design. Two dose groups were set up: low dose group (7×109 VG/ eye, 0.05ml)&#xD;
        and high dose group (3.5×1010 VG/ eye, 0.05ml). Among them, 3 to 6 subjects were enrolled in&#xD;
        low-dose group and 6 subjects were enrolled in high-dose group.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 30, 2027</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2025</primary_completion_date>
    <phase>N/A</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>Adverse Event</measure>
      <time_frame>4 weeks</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change of mean BCVA score on the ETDRS visual acuity scale from baseline.</measure>
      <time_frame>4 weeks、24 weeks、52 weeks</time_frame>
      <description>Changes of BCVA scores on the ETDRS visual acuity chart of the study eye from baseline at 4, 24 and 52 weeks after treatment with LX109.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in mean eye CST from baseline at 4, 24 and 52 weeks after LX109 treatment were studied.</measure>
      <time_frame>4 weeks、24 weeks、52 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The time after LX109 treatment to the first salvage treatment.</measure>
      <time_frame>52 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of subjects receiving salvage treatment in the study eye at 24 weeks and 52 weeks after treatment with LX109.</measure>
      <time_frame>24 weeks、52 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The number of times the eye received salvage treatment at 24 weeks and 52 weeks after treatment with LX109 was studied.</measure>
      <time_frame>24 weeks、52 weeks</time_frame>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">12</enrollment>
    <condition>To Evaluate the Safety and Tolerability of Intravitreal Injection of LX109 in Patients With nAMD</condition>
    <arm_group>
      <arm_group_label>LX109</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>LX109</intervention_name>
      <description>LX109 gene injection Specification: 0.2ml/bottle, 1.4×1012VG/ml Administration route: intravitreal injection, injection volume 0.05ml/eye</description>
      <arm_group_label>LX109</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  1) Informed consent must be signed before all assessments; 2) Male or female patients&#xD;
               ≥50 years of age; 3) To investigate the presence of active CNV secondary to nAMD&#xD;
               (occult or micromenorrhea) in the eye 4) When studying the baseline of the eye, use&#xD;
               the ETDRS eye chart to test the BCVA of 19 to 73 letters (approximately equivalent to&#xD;
               decimal notation) Recorded visual acuity 0.05-0.5); 5) Study eyes received at least 2&#xD;
               anti-VEGF treatments within 6 months. Note: For all subjects, only one eye was used as&#xD;
               the &quot;study eye&quot; (i.e. the study eye receiving treatment). If both eyes of the subject&#xD;
               meet the inclusion criteria, the eye with poor baseline vision will be selected as the&#xD;
               study eye, or the eye with better vision may be selected for medical reasons or&#xD;
               ethical requirements.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  1. In the investigator's judgment, concomitant eye diseases of the study eye at&#xD;
               screening or baseline may cause subjects to fail to respond to study therapy or&#xD;
               confuse the interpretation of study findings. For example, diabetic retinopathy,&#xD;
               retinal vein obstruction, retinal retinal detachment, macular hiatus (stage 3 or 4),&#xD;
               uveitis, vitreous macular traction affecting central vision, macular anterior membrane&#xD;
               involving macular fovea or damaging macular structure, equivalent spherical lens&#xD;
               ≤-8.00D of the study eye, etc.&#xD;
  &#xD;
               2. To investigate the presence of subretinal hyperreflective substance (SHRM)&#xD;
               involving the fovea except CNV lesions; 3. Central serous chorioretinopathy (CSC) was&#xD;
               confirmed in the study eyes at any time; 4. Study retinal detachment in the eye at any&#xD;
               time; 5. Non-study eye BCV A less than decimal recorded visual acuity 0.05(&lt;19 ETDRS&#xD;
               letters); 6. The presence of uncontrolled glaucoma (defined as intraocular pressure&#xD;
               ≥25mmHg after standard treatment) in the study eye; 7. Active intraocular or&#xD;
               periocular inflammation or infection in the study eye or non-study eye; 8. To&#xD;
               investigate the presence of CNV or macular edema secondary to causes other than AMD;&#xD;
               9. In the study, the refractive medium of the eye is seriously cloudy or the pupil&#xD;
               cannot be sufficiently dilated, affecting BCVA or causing insufficient acquisition&#xD;
               Clear eye imaging data, such as OCT, FFA, and fundus photography, affect researchers'&#xD;
               observation of safety and efficacy.&#xD;
  &#xD;
          Eye Treatment： 10. Internal eye surgery, such as vitrectomy, cataract phacoemulsification,&#xD;
          trabeculectomy, or other filtering surgery, was performed within 3 months prior to baseline&#xD;
          screening or study eye screening; 11. Study eyes screened or treated with intravitreal drug&#xD;
          injections or drug-containing intraocular implants other than anti-VEGF drugs, such as&#xD;
          intraocular corticosteroids, within 6 months prior to baseline; 12. Research eye or&#xD;
          systemic have received gene therapy; 13. Study eyes screened or treated with macular laser&#xD;
          photocoagulation or photodynamic therapy (PDT) or full vision membrane laser&#xD;
          photocoagulation within 3 months prior to baseline; 14. Study eyes were screened or&#xD;
          underwent YAG laser posterior capsulectomy or laser trabeculectomy or laser periiridectomy&#xD;
          within 1 month prior to baseline&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>50 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <reference>
      <citation>Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014 Feb;2(2):e106-16. doi: 10.1016/S2214-109X(13)70145-1. Epub 2014 Jan 3.</citation>
      <PMID>25104651</PMID>
    </reference>
    <reference>
      <citation>Yang K, Liang YB, Gao LQ, Peng Y, Shen R, Duan XR, Friedman DS, Sun LP, Mitchell P, Wang NL, Wong TY, Wang JJ. Prevalence of age-related macular degeneration in a rural Chinese population: the Handan Eye Study. Ophthalmology. 2011 Jul;118(7):1395-401. doi: 10.1016/j.ophtha.2010.12.030. Epub 2011 Mar 27.</citation>
      <PMID>21444116</PMID>
    </reference>
    <reference>
      <citation>Ye H, Zhang Q, Liu X, Cai X, Yu W, Yu S, Wang T, Lu W, Li X, Jin H, Hu Y, Kang X, Zhao P. Prevalence of age-related macular degeneration in an elderly urban chinese population in China: the Jiangning Eye Study. Invest Ophthalmol Vis Sci. 2014 Sep 4;55(10):6374-80. doi: 10.1167/iovs.14-14899.</citation>
      <PMID>25190650</PMID>
    </reference>
    <reference>
      <citation>van Lookeren Campagne M, LeCouter J, Yaspan BL, Ye W. Mechanisms of age-related macular degeneration and therapeutic opportunities. J Pathol. 2014 Jan;232(2):151-64. doi: 10.1002/path.4266.</citation>
      <PMID>24105633</PMID>
    </reference>
    <reference>
      <citation>Mitchell P, Liew G, Gopinath B, Wong TY. Age-related macular degeneration. Lancet. 2018 Sep 29;392(10153):1147-1159. doi: 10.1016/S0140-6736(18)31550-2.</citation>
      <PMID>30303083</PMID>
    </reference>
    <reference>
      <citation>Khandhadia S, Cherry J, Lotery AJ. Age-related macular degeneration. Adv Exp Med Biol. 2012;724:15-36. doi: 10.1007/978-1-4614-0653-2_2.</citation>
      <PMID>22411231</PMID>
    </reference>
    <reference>
      <citation>Fleckenstein M, Keenan TDL, Guymer RH, Chakravarthy U, Schmitz-Valckenberg S, Klaver CC, Wong WT, Chew EY. Age-related macular degeneration. Nat Rev Dis Primers. 2021 May 6;7(1):31. doi: 10.1038/s41572-021-00265-2.</citation>
      <PMID>33958600</PMID>
    </reference>
    <reference>
      <citation>Holz FG, Tadayoni R, Beatty S, Berger A, Cereda MG, Cortez R, Hoyng CB, Hykin P, Staurenghi G, Heldner S, Bogumil T, Heah T, Sivaprasad S. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. Br J Ophthalmol. 2015 Feb;99(2):220-6. doi: 10.1136/bjophthalmol-2014-305327. Epub 2014 Sep 5.</citation>
      <PMID>25193672</PMID>
    </reference>
    <reference>
      <citation>Cabral T, Lima LH, Mello LGM, Polido J, Correa EP, Oshima A, Duong J, Serracarbassa P, Regatieri CV, Mahajan VB, Belfort R Jr. Bevacizumab Injection in Patients with Neovascular Age-Related Macular Degeneration Increases Angiogenic Biomarkers. Ophthalmol Retina. 2018 Jan;2(1):31-37. doi: 10.1016/j.oret.2017.04.004.</citation>
      <PMID>29376143</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
      <investigator_full_name>Xiaodong Sun</investigator_full_name>
      <investigator_title>Assessor</investigator_title>
    </responsible_party>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT06022744
  org study id: SHGH-LX109
  nct id: NCT06022744
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  To evaluate the safety and tolerability of intravitreal injection of LX109 in patients with
        nAMD.
  In this study, 9 to 12 participants were enrolled in an open monocular, single dose
        escalation study design. Two dose groups were set up: low dose group (7×109 VG/ eye, 0.05ml)
        and high dose group (3.5×1010 VG/ eye, 0.05ml). Among them, 3 to 6 subjects were enrolled in
        low-dose group and 6 subjects were enrolled in high-dose group.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Adverse Event
  time frame: 4 weeks
  measure: Change of mean BCVA score on the ETDRS visual acuity scale from baseline.
  time frame: 4 weeks、24 weeks、52 weeks
  description: Changes of BCVA scores on the ETDRS visual acuity chart of the study eye from baseline at 4, 24 and 52 weeks after treatment with LX109.
  measure: Changes in mean eye CST from baseline at 4, 24 and 52 weeks after LX109 treatment were studied.
  time frame: 4 weeks、24 weeks、52 weeks
  measure: The time after LX109 treatment to the first salvage treatment.
  time frame: 52 weeks
  measure: Proportion of subjects receiving salvage treatment in the study eye at 24 weeks and 52 weeks after treatment with LX109.
  time frame: 24 weeks、52 weeks
  measure: The number of times the eye received salvage treatment at 24 weeks and 52 weeks after treatment with LX109 was studied.
  time frame: 24 weeks、52 weeks
  arm group label: LX109
  arm group type: Experimental
  intervention type: Drug
  intervention name: LX109
  description: LX109 gene injection Specification: 0.2ml/bottle, 1.4×1012VG/ml Administration route: intravitreal injection, injection volume 0.05ml/eye
  arm group label: LX109
  criteria: 
  gender: All
  minimum age: 50 Years
  maximum age: N/A
  healthy volunteers: No
  citation: Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014 Feb;2(2):e106-16. doi: 10.1016/S2214-109X(13)70145-1. Epub 2014 Jan 3.
  PMID: 25104651
  citation: Yang K, Liang YB, Gao LQ, Peng Y, Shen R, Duan XR, Friedman DS, Sun LP, Mitchell P, Wang NL, Wong TY, Wang JJ. Prevalence of age-related macular degeneration in a rural Chinese population: the Handan Eye Study. Ophthalmology. 2011 Jul;118(7):1395-401. doi: 10.1016/j.ophtha.2010.12.030. Epub 2011 Mar 27.
  PMID: 21444116
  citation: Ye H, Zhang Q, Liu X, Cai X, Yu W, Yu S, Wang T, Lu W, Li X, Jin H, Hu Y, Kang X, Zhao P. Prevalence of age-related macular degeneration in an elderly urban chinese population in China: the Jiangning Eye Study. Invest Ophthalmol Vis Sci. 2014 Sep 4;55(10):6374-80. doi: 10.1167/iovs.14-14899.
  PMID: 25190650
  citation: van Lookeren Campagne M, LeCouter J, Yaspan BL, Ye W. Mechanisms of age-related macular degeneration and therapeutic opportunities. J Pathol. 2014 Jan;232(2):151-64. doi: 10.1002/path.4266.
  PMID: 24105633
  citation: Mitchell P, Liew G, Gopinath B, Wong TY. Age-related macular degeneration. Lancet. 2018 Sep 29;392(10153):1147-1159. doi: 10.1016/S0140-6736(18)31550-2.
  PMID: 30303083
  citation: Khandhadia S, Cherry J, Lotery AJ. Age-related macular degeneration. Adv Exp Med Biol. 2012;724:15-36. doi: 10.1007/978-1-4614-0653-2_2.
  PMID: 22411231
  citation: Fleckenstein M, Keenan TDL, Guymer RH, Chakravarthy U, Schmitz-Valckenberg S, Klaver CC, Wong WT, Chew EY. Age-related macular degeneration. Nat Rev Dis Primers. 2021 May 6;7(1):31. doi: 10.1038/s41572-021-00265-2.
  PMID: 33958600
  citation: Holz FG, Tadayoni R, Beatty S, Berger A, Cereda MG, Cortez R, Hoyng CB, Hykin P, Staurenghi G, Heldner S, Bogumil T, Heah T, Sivaprasad S. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. Br J Ophthalmol. 2015 Feb;99(2):220-6. doi: 10.1136/bjophthalmol-2014-305327. Epub 2014 Sep 5.
  PMID: 25193672
  citation: Cabral T, Lima LH, Mello LGM, Polido J, Correa EP, Oshima A, Duong J, Serracarbassa P, Regatieri CV, Mahajan VB, Belfort R Jr. Bevacizumab Injection in Patients with Neovascular Age-Related Macular Degeneration Increases Angiogenic Biomarkers. Ophthalmol Retina. 2018 Jan;2(1):31-37. doi: 10.1016/j.oret.2017.04.004.
  PMID: 29376143
  responsible party type: Principal Investigator
  investigator affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
  investigator full name: Xiaodong Sun
  investigator title: Assessor
  sharing ipd: No