<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/NCT03748784</url>
  </required_header>
  <id_info>
    <org_study_id>ADVM-022-01</org_study_id>
    <nct_id>NCT03748784</nct_id>
  </id_info>
  <brief_title>ADVM-022 Intravitreal Gene Therapy for Wet AMD</brief_title>
  <acronym>OPTIC</acronym>
  <official_title>An Open Label Phase 1 Study of ADVM-022 (AAV.7m8-aflibercept) in Neovascular (Wet) Age-Related Macular Degeneration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Adverum Biotechnologies, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Adverum Biotechnologies, 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product developed for the treatment of&#xD;
      neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is a serious condition&#xD;
      and the leading cause of blindness in the elderly. The available therapies for treating wet&#xD;
      AMD require life-long intravitreal (IVT) injections every 4-12 weeks to maintain efficacy. A&#xD;
      one-time IVT administration of ADVM-022 has the potential to treat wet AMD by providing&#xD;
      durable expression of therapeutic levels of intraocular anti-VEGF protein (aflibercept) and&#xD;
      maintaining the vision of patients. ADVM-022 is designed to reduce the current treatment&#xD;
      burden which often results in undertreatment and vision loss in patients with wet AMD&#xD;
      receiving anti-VEGF therapy in clinical practice.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This open-label, multicenter, dose-ranging study will evaluate 2 dose levels in up to 30&#xD;
      subjects (15 per dose) with active choroidal neovascularization (CNV) secondary to AMD.&#xD;
      Subjects who are under active anti-VEGF treatment and have demonstrated a meaningful response&#xD;
      to anti-VEGF therapy will be considered for participation in this study. The primary endpoint&#xD;
      for this study is safety and tolerability of ADVM-022. All subjects will continue to be&#xD;
      assessed for 104 weeks following treatment with ADVM-022.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 14, 2018</start_date>
  <completion_date type="Actual">June 22, 2022</completion_date>
  <primary_completion_date type="Actual">June 22, 2022</primary_completion_date>
  <phase>Phase 1</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>Open-label, dose-ranging clinical study to evaluate the safety and tolerability of ADVM-022 in subjects with wet AMD.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Type, severity, and incidence of ocular and systemic adverse events (AEs)</measure>
    <time_frame>104 weeks</time_frame>
    <description>Type, severity, and incidence of ocular and systemic adverse events (AEs)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in best corrected visual acuity (BCVA)</measure>
    <time_frame>104 weeks</time_frame>
    <description>Change in best corrected visual acuity (BCVA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in central subfield thickness (CST) and macular volume measured by SD-OCT</measure>
    <time_frame>104 weeks</time_frame>
    <description>Change in central subfield thickness (CST) and macular volume measured by SD-OCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects requiring anti-VEGF injections over time</measure>
    <time_frame>104 weeks</time_frame>
    <description>Percentage of subjects requiring anti-VEGF injections over time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean number of anti-VEGF injections over time</measure>
    <time_frame>104 weeks</time_frame>
    <description>Mean number of anti-VEGF injections over time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects without intraretinal fluid over time</measure>
    <time_frame>104 weeks</time_frame>
    <description>Percentage of subjects without intraretinal fluid over time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects without subretinal fluid over time</measure>
    <time_frame>104 weeks</time_frame>
    <description>Percentage of subjects without subretinal fluid over time</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Wet Age-related Macular Degeneration</condition>
  <condition>Neovascular Age-related Macular Degeneration</condition>
  <arm_group>
    <arm_group_label>Dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6E11 vg of ADVM-022</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2E11 vg of ADVM-022</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ADVM-022</intervention_name>
    <description>ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept</description>
    <arm_group_label>Dose 1</arm_group_label>
    <arm_group_label>Dose 2</arm_group_label>
    <other_name>AAV.7m8-aflibercept</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 50&#xD;
&#xD;
          -  Diagnosis of neovascular (wet) AMD&#xD;
&#xD;
          -  BCVA ETDRS Snellen equivalent between ≤20/32 and ≥20/320 for each cohort&#xD;
&#xD;
          -  Subjects must be under active anti-VEGF treatment for wAMD and received a minimum of 2&#xD;
             injections within 4 months prior to screening&#xD;
&#xD;
          -  Demonstrated a meaningful response to anti-VEGF therapy&#xD;
&#xD;
          -  Willing and able to provide consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of retinal disease in the study eye other than wet AMD&#xD;
&#xD;
          -  Fibrosis or atrophy, retinal epithelial tear in the center of the fovea in the study&#xD;
             eye, or any condition preventing visual acuity improvement&#xD;
&#xD;
          -  History of retinal detachment (with or without repair) in the study eye&#xD;
&#xD;
          -  History of vitrectomy, trabeculectomy, or other filtration surgery in the study eye&#xD;
&#xD;
          -  Uncontrolled glaucoma in the study eye&#xD;
&#xD;
          -  Any prior treatment with photodynamic therapy or retinal laser for the treatment of&#xD;
             wet AMD and any previous therapeutic radiation in the region of the study eye&#xD;
&#xD;
          -  Any previous intraocular or periocular surgery on the study eye within 6 months&#xD;
&#xD;
          -  Acute coronary syndrome, myocardial infarction or coronary artery revascularization,&#xD;
             CVA, TIA in the last 6 months&#xD;
&#xD;
          -  Uncontrolled hypertension defined as average SBP ≥160 mmHg or an average DBP ≥100 mmHg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>OPTIC Medical Monitor</last_name>
    <role>Study Chair</role>
    <affiliation>Adverum Biotechnologies, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Adverum Clinical Site</name>
      <address>
        <city>Bakersfield</city>
        <state>California</state>
        <zip>93309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adverum Clinical Site</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adverum Clinical Site</name>
      <address>
        <city>Golden</city>
        <state>Colorado</state>
        <zip>80401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adverum Clinical Site</name>
      <address>
        <city>Deerfield Beach</city>
        <state>Florida</state>
        <zip>33064</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adverum Clinical Site</name>
      <address>
        <city>Reno</city>
        <state>Nevada</state>
        <zip>89502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adverum Clinical Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adverum Clinical Site</name>
      <address>
        <city>West Columbia</city>
        <state>South Carolina</state>
        <zip>29169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adverum Clinical Site</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adverum Clinical Site</name>
      <address>
        <city>Abilene</city>
        <state>Texas</state>
        <zip>79606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adverum Clinical Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adverum Clinical Site</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77384</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>August 4, 2023</last_update_submitted>
  <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Choroidal Neovascularizatio</keyword>
  <keyword>ADVM-022</keyword>
  <keyword>CNV</keyword>
  <keyword>ADVM-022-01</keyword>
  <keyword>AAV.7m8</keyword>
  <keyword>Anti-VEGF therapy</keyword>
  <keyword>Blindness</keyword>
  <keyword>Gene therapy</keyword>
  <keyword>Aflibercept (Eylea)</keyword>
  <keyword>Age-Related Macular Degeneration</keyword>
  <keyword>Wet Macular Degeneration</keyword>
  <keyword>Retinal Degeneration</keyword>
  <keyword>Retinal Diseases</keyword>
  <keyword>Eye Diseases</keyword>
  <keyword>AAV Vector</keyword>
  <keyword>Adverum</keyword>
  <keyword>wAMD</keyword>
  <keyword>AMD</keyword>
  <keyword>wet AMD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Degeneration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aflibercept</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03748784
org study id: ADVM-022-01
nct id: NCT03748784
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product developed for the treatment of
      neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is a serious condition
      and the leading cause of blindness in the elderly. The available therapies for treating wet
      AMD require life-long intravitreal (IVT) injections every 4-12 weeks to maintain efficacy. A
      one-time IVT administration of ADVM-022 has the potential to treat wet AMD by providing
      durable expression of therapeutic levels of intraocular anti-VEGF protein (aflibercept) and
      maintaining the vision of patients. ADVM-022 is designed to reduce the current treatment
      burden which often results in undertreatment and vision loss in patients with wet AMD
      receiving anti-VEGF therapy in clinical practice.
This open-label, multicenter, dose-ranging study will evaluate 2 dose levels in up to 30
      subjects (15 per dose) with active choroidal neovascularization (CNV) secondary to AMD.
      Subjects who are under active anti-VEGF treatment and have demonstrated a meaningful response
      to anti-VEGF therapy will be considered for participation in this study. The primary endpoint
      for this study is safety and tolerability of ADVM-022. All subjects will continue to be
      assessed for 104 weeks following treatment with ADVM-022.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Open-label, dose-ranging clinical study to evaluate the safety and tolerability of ADVM-022 in subjects with wet AMD.
primary purpose: Treatment
masking: None (Open Label)
measure: Type, severity, and incidence of ocular and systemic adverse events (AEs)
time frame: 104 weeks
description: Type, severity, and incidence of ocular and systemic adverse events (AEs)
measure: Change in best corrected visual acuity (BCVA)
time frame: 104 weeks
description: Change in best corrected visual acuity (BCVA)
measure: Change in central subfield thickness (CST) and macular volume measured by SD-OCT
time frame: 104 weeks
description: Change in central subfield thickness (CST) and macular volume measured by SD-OCT
measure: Percentage of subjects requiring anti-VEGF injections over time
time frame: 104 weeks
description: Percentage of subjects requiring anti-VEGF injections over time
measure: Mean number of anti-VEGF injections over time
time frame: 104 weeks
description: Mean number of anti-VEGF injections over time
measure: Percentage of subjects without intraretinal fluid over time
time frame: 104 weeks
description: Percentage of subjects without intraretinal fluid over time
measure: Percentage of subjects without subretinal fluid over time
time frame: 104 weeks
description: Percentage of subjects without subretinal fluid over time
arm group label: Dose 1
arm group type: Experimental
description: 6E11 vg of ADVM-022
arm group label: Dose 2
arm group type: Experimental
description: 2E11 vg of ADVM-022
intervention type: Biological
intervention name: ADVM-022
description: ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept
arm group label: Dose 1
arm group label: Dose 2
other name: AAV.7m8-aflibercept
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: OPTIC Medical Monitor
role: Study Chair
affiliation: Adverum Biotechnologies, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: Aflibercept