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/NCT05984927</url>
    </required_header>
    <id_info>
      <org_study_id>NG101WA-01</org_study_id>
      <nct_id>NCT05984927</nct_id>
    </id_info>
    <brief_title>NG101 AAV Gene Therapy in Subjects With Wet Age-Related Macular Degeneration</brief_title>
    <official_title>A Phase 1/2a Open-label Study to Evaluate Safety, Tolerability and Preliminary Efficacy of NG101 AAV Gene Therapy in Subjects With Wet Age-Related Macular Degeneration</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Neuracle Genetics, Inc</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>ORA, Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Neuracle Genetics, Inc</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study will evaluate the safety, tolerability, and preliminary efficacy of NG101 AAV gene&#xD;
        therapy administered by subretinal injections into a single selected eye as a single selected&#xD;
        dose for patients with wet age-related macular degeneration (wAMD).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a Phase 1/2a, multicenter, open-label, dose escalation study to evaluate the safety,&#xD;
        tolerability, and preliminary efficacy of NG101 AAV gene therapy, administered by subretinal&#xD;
        injection in patients with active wAMD symptoms. The study will be conducted at approximately&#xD;
        6 sites in Canada and the USA.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">January 2030</completion_date>
    <primary_completion_date type="Anticipated">January 2025</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>Dose Escalation Study with 3 dose cohorts</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Adverse Events</measure>
      <time_frame>Day 0 (pre-treatment) and Week 24</time_frame>
      <description>Incidence and severity of ocular and non-ocular adverse events (AEs) for each cohort</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Ocular and Non -Ocular Adverse Events after week 24</measure>
      <time_frame>Day 0 (pre-treatment) and from Week 24 to Week 260</time_frame>
      <description>Incidence and severity of ocular and non-ocular AEs after Week 24 to Week 260 for each cohort</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Systemic Immunogenic Response</measure>
      <time_frame>Day 0, Week 12, 24, 52, and 104</time_frame>
      <description>Change in concentration of expressed aflibercept protein in vitreous samples</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Systemic Immunogenic Response</measure>
      <time_frame>Day -7 Weeks 4, 12, and 104</time_frame>
      <description>Change in concentration of expressed aflibercept protein in serum samples</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Systemic Immunogenic Response</measure>
      <time_frame>Day -7, Week 4, and week 12</time_frame>
      <description>Change in AAV vector (NG101) genome copies as measured by PCR in blood samples</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Systemic Immunogenic Response</measure>
      <time_frame>Day -7, Week 4, week 8, week 12, week 24, week 52, and week 104</time_frame>
      <description>Change in concentration of Anti-NG101 Transgene protein antibodies, Anti-AAV8 Neutralizing antibodies, and Anti-AAV8 Antibodies in serum samples</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Signs of CNV Activity</measure>
      <time_frame>At every visit from Screening through Week 104</time_frame>
      <description>Change of 1 or more signs of CNV activity assessed by Optical coherence tomography</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Central Retinal Thickness (CRT)</measure>
      <time_frame>from Screening to Weeks 260</time_frame>
      <description>Change in CRT assessed with OCT</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Best Corrected Visual Acuity (BCVA)</measure>
      <time_frame>from Screening to Weeks 260</time_frame>
      <description>Change in BCVA assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) scale</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative Number of Rescue Therapy Injections</measure>
      <time_frame>From Week 24 to Week 260</time_frame>
      <description>The cumulative number of rescue therapy injections per subject to maintain CNV control</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">18</enrollment>
    <condition>Age-Related Macular Degeneration</condition>
    <arm_group>
      <arm_group_label>NG101 Gene Therapy Group 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single subretinal injection of 1x10^9 vector genomes of NG101 AAV gene therapy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>NG101 Gene Therapy Group 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single subretinal injection of 3x10^9 vector genomes of NG101 AAV gene therapy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>NG101 Gene Therapy Group 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single subretinal injection of 8x10^9 vector genomes of NG101 AAV gene therapy</description>
    </arm_group>
    <intervention>
      <intervention_type>Genetic</intervention_type>
      <intervention_name>NG101 AAV gene therapy</intervention_name>
      <description>Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector</description>
      <arm_group_label>NG101 Gene Therapy Group 1</arm_group_label>
      <arm_group_label>NG101 Gene Therapy Group 2</arm_group_label>
      <arm_group_label>NG101 Gene Therapy Group 3</arm_group_label>
      <other_name>NG101</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Subjects ≥ 50 and ≤ 89 years of age with a diagnosis of active subfoveal CNV secondary&#xD;
               to wAMD in the Study Eye&#xD;
  &#xD;
            2. BCVA between 20/63 and 20/400 in the Study Eye, with BCVA decrement primarily&#xD;
               attributable to wAMD&#xD;
  &#xD;
            3. Administration of at least 3 anti-VEGF injections in the past 6 months, the most&#xD;
               recent of which was within 2 months prior to Screening.&#xD;
  &#xD;
            4. Must be pseudo phakic (status post cataract surgery) in the Study Eye&#xD;
  &#xD;
            5. Female subjects must be either: (1) of non-childbearing potential; or (2) of&#xD;
               childbearing potential and using an acceptable method of birth control with a negative&#xD;
               pregnancy test:&#xD;
  &#xD;
            6. Willing and able to provide written, signed informed consent after the nature of the&#xD;
               study has been explained and prior to the performance of any study-related procedures&#xD;
  &#xD;
            7. Willingness and ability to comply with schedule for follow-up visits and postoperative&#xD;
               evaluations&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. CNV or macular edema in the Study Eye secondary to any causes other than AMD&#xD;
  &#xD;
            2. Any condition preventing visual acuity improvement in the Study Eye, e.g., fibrosis,&#xD;
               atrophy, or retinal pigment epithelial tear in the center of the macula&#xD;
  &#xD;
            3. Any ophthalmic condition that precludes adequate ophthalmic examination or requires&#xD;
               ancillary testing&#xD;
  &#xD;
            4. Retinal detachment or history of retinal detachment in the Study Eye&#xD;
  &#xD;
            5. Active uncontrolled glaucoma with intraocular pressure (IOP) ≥ 30 mmHg despite&#xD;
               treatment with more than 2 glaucoma medications, advanced glaucoma with cup-to-disc&#xD;
               ratio of ≥ 0.9, visual field defects secondary to glaucoma that involve the macula,&#xD;
               and/or optic atrophy from glaucoma&#xD;
  &#xD;
            6. History of intravitreal therapy in the Study Eye, such as intravitreal steroid&#xD;
               injection or an investigational product, other than anti-VEGF therapy, in the 6 months&#xD;
               prior to Screening&#xD;
  &#xD;
            7. History of vitrectomy, trabeculectomy, glaucoma tube-shunt procedure, minimally&#xD;
               invasive glaucoma surgery (MIGS) device, or other filtration surgery in the Study Eye&#xD;
  &#xD;
            8. Any prior treatment with photodynamic therapy or retinal laser for the treatment of&#xD;
               wAMD&#xD;
  &#xD;
            9. Any prior therapeutic radiation in the region of the Study Eye such as whole brain&#xD;
               radiation, proton beam radiation, gamma knife treatment, or plaque brachytherapy&#xD;
  &#xD;
           10. Any previous intraocular or refractive surgery on the Study Eye within 6 months&#xD;
  &#xD;
           11. Any previous gene therapy in the Study Eye&#xD;
  &#xD;
           12. Presence of an ocular implant in the Study Eye at Screening, excluding intraocular&#xD;
               lens and custom flex iris prosthesis&#xD;
  &#xD;
           13. Any diabetic retinopathy or other retinal vascular disease including retinal vein&#xD;
               occlusion, retinal artery occlusion, retinal arterial macro aneurysm, ocular ischemic&#xD;
               syndrome, retinal vasculitis, vitritis, posterior uveitis&#xD;
  &#xD;
           14. Any medically uncontrolled diabetes, defined as HbA1C &gt; 8.0&#xD;
  &#xD;
           15. History of ocular melanoma&#xD;
  &#xD;
           16. History of any known inherited retinal disease&#xD;
  &#xD;
           17. Currently taking any anticoagulant therapy, which is deemed medically necessary and&#xD;
               cannot be permanently stopped at least 2 weeks prior to NG101 injection, excluding&#xD;
               prophylactic low-dose aspirin therapy&#xD;
  &#xD;
           18. Any underlying systemic diseases as severe cardiovascular, cerebrovascular, and&#xD;
               neurodegenerative diseases, including active malignancy and immunocompromised&#xD;
               conditions.&#xD;
  &#xD;
           19. Active hepatitis B or C&#xD;
  &#xD;
           20. History of human immunodeficiency virus (HIV), active tuberculosis, and/or syphilis&#xD;
  &#xD;
           21. Any significant illness that would preclude study compliance and follow-up&#xD;
  &#xD;
           22. Subjects who, in the Investigator's opinion, lack the mental capacity to provide&#xD;
               written informed consent for study participation&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>50 Years</minimum_age>
      <maximum_age>89 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Christopher D Riemann, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Neuracle Genetics, Inc. Medical Director</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Sheila Yi</last_name>
      <phone>770-296-7301</phone>
      <email>wetamd@neuraclegen.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Hea Reung Park</last_name>
      <email>wetamd@neuraclegen.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Vitreous Retina Macula Specialists of Toronto</name>
        <address>
          <city>Toronto</city>
          <state>Ontario</state>
          <zip>M8X 2X3</zip>
          <country>Canada</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Tatjana Sukovic</last_name>
        <email>tatjana@vrmto.com</email>
      </contact>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 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>Wet macular degeneration</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>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/NCT05984927
  org study id: NG101WA-01
  nct id: NCT05984927
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  This study will evaluate the safety, tolerability, and preliminary efficacy of NG101 AAV gene
        therapy administered by subretinal injections into a single selected eye as a single selected
        dose for patients with wet age-related macular degeneration (wAMD).
  This is a Phase 1/2a, multicenter, open-label, dose escalation study to evaluate the safety,
        tolerability, and preliminary efficacy of NG101 AAV gene therapy, administered by subretinal
        injection in patients with active wAMD symptoms. The study will be conducted at approximately
        6 sites in Canada and the USA.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  intervention model description: Dose Escalation Study with 3 dose cohorts
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Adverse Events
  time frame: Day 0 (pre-treatment) and Week 24
  description: Incidence and severity of ocular and non-ocular adverse events (AEs) for each cohort
  measure: Ocular and Non -Ocular Adverse Events after week 24
  time frame: Day 0 (pre-treatment) and from Week 24 to Week 260
  description: Incidence and severity of ocular and non-ocular AEs after Week 24 to Week 260 for each cohort
  measure: Systemic Immunogenic Response
  time frame: Day 0, Week 12, 24, 52, and 104
  description: Change in concentration of expressed aflibercept protein in vitreous samples
  measure: Systemic Immunogenic Response
  time frame: Day -7 Weeks 4, 12, and 104
  description: Change in concentration of expressed aflibercept protein in serum samples
  measure: Systemic Immunogenic Response
  time frame: Day -7, Week 4, and week 12
  description: Change in AAV vector (NG101) genome copies as measured by PCR in blood samples
  measure: Systemic Immunogenic Response
  time frame: Day -7, Week 4, week 8, week 12, week 24, week 52, and week 104
  description: Change in concentration of Anti-NG101 Transgene protein antibodies, Anti-AAV8 Neutralizing antibodies, and Anti-AAV8 Antibodies in serum samples
  measure: Signs of CNV Activity
  time frame: At every visit from Screening through Week 104
  description: Change of 1 or more signs of CNV activity assessed by Optical coherence tomography
  measure: Central Retinal Thickness (CRT)
  time frame: from Screening to Weeks 260
  description: Change in CRT assessed with OCT
  measure: Best Corrected Visual Acuity (BCVA)
  time frame: from Screening to Weeks 260
  description: Change in BCVA assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) scale
  measure: Cumulative Number of Rescue Therapy Injections
  time frame: From Week 24 to Week 260
  description: The cumulative number of rescue therapy injections per subject to maintain CNV control
  arm group label: NG101 Gene Therapy Group 1
  arm group type: Experimental
  description: Single subretinal injection of 1x10^9 vector genomes of NG101 AAV gene therapy
  arm group label: NG101 Gene Therapy Group 2
  arm group type: Experimental
  description: Single subretinal injection of 3x10^9 vector genomes of NG101 AAV gene therapy
  arm group label: NG101 Gene Therapy Group 3
  arm group type: Experimental
  description: Single subretinal injection of 8x10^9 vector genomes of NG101 AAV gene therapy
  intervention type: Genetic
  intervention name: NG101 AAV gene therapy
  description: Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector
  arm group label: NG101 Gene Therapy Group 1
  arm group label: NG101 Gene Therapy Group 2
  arm group label: NG101 Gene Therapy Group 3
  other name: NG101
  criteria: 
  gender: All
  minimum age: 50 Years
  maximum age: 89 Years
  healthy volunteers: No
  last name: Christopher D Riemann, MD
  role: Principal Investigator
  affiliation: Neuracle Genetics, Inc. Medical Director
  last name: Sheila Yi
  phone: 770-296-7301
  email: wetamd@neuraclegen.com
  last name: Hea Reung Park
  email: wetamd@neuraclegen.com
  facility: 
  status: Recruiting
  contact: 
  country: Canada
  responsible party type: Sponsor
  mesh term: Macular Degeneration