<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/NCT01722045</url>
  </required_header>
  <id_info>
    <org_study_id>VGFTe-AMD-1124</org_study_id>
    <nct_id>NCT01722045</nct_id>
  </id_info>
  <brief_title>Study to Assess Best Corrected Visual Acuity (BCVA) in Patients With Neovascular Age-Related Macular Degeneration (AMD) Who Are Administered VEGF Trap-Eye (Intravitreal Aflibercept Injection)</brief_title>
  <acronym>RE-VIEW</acronym>
  <official_title>An Open-Label Study of the Efficacy, Safety, and Tolerability of Intravitreal Administration of VEGF Trap-Eye (Intravitreal Aflibercept Injection) in Patients With Neovascular Age-Related Macular Degeneration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Regeneron Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 4, open-label, single arm, multicenter, clinical study in patients with&#xD;
      neovascular AMD designed to evaluate the efficacy and safety of Intravitreal Aflibercept&#xD;
      Injection (IAI) administered over 2 years , and to provide clinical information from the&#xD;
      first year in the trial evaluating the adverse effects, if any, on the corneal endothelium&#xD;
      following administration of IAI.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <phase>Phase 4</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>Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score From Baseline to Week 100 - Last Observation Carried Forward (LOCF)</measure>
    <time_frame>Baseline to Week 100</time_frame>
    <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. LOCF approach was used if any ETDRS letter score was missed after start of treatment, but baseline data were not carried forward. No formal statistical analyses were performed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Whose Optical Coherence Tomography (OCT) Status Was &quot;Dry&quot; at Week 52 and at Week 100 (LOCF)</measure>
    <time_frame>Baseline to Week 100</time_frame>
    <description>Retinal fluid status was evaluated using spectral domain OCT on the study eye at every study visit. Last observation carried forward (LOCF) method was used to impute missing data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Gained ≥15 ETDRS Letters Compared With Baseline at Week 52 and Week 100 (LOCF)</measure>
    <time_frame>At week 52 and At week 100</time_frame>
    <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. LOCF approach was used if any ETDRS letter score was missed after start of treatment, but baseline data were not carried forward. No formal statistical analyses were performed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Best Corrected Visual Acuity Score Through Week 52 (LOCF)</measure>
    <time_frame>Baseline to Week 52</time_frame>
    <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Gained ≥0, ≥5, ≥10, or ≥30 Letters From Baseline in BCVA Through Week 100 (LOCF)</measure>
    <time_frame>Baseline to Week 100</time_frame>
    <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Who Lost &gt;0, ≥5, ≥10, or ≥15 Letters From Baseline in BCVA Through Week 100 (LOCF)</measure>
    <time_frame>Baseline to Week 100</time_frame>
    <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Percent Change From Baseline in Corneal Endothelial Cell Density (ECD) at Week 24 and Week 52 in the Study Eye and the Fellow Eye - Endothelial Cell Density Evaluable Set (EES)</measure>
    <time_frame>At week 24 and At week 52</time_frame>
    <description>EES included all eligible patients who were treated in the study eye, untreated in the fellow eye, had baseline specular microscopy image in both eyes, and completed week 52 evaluation in both eyes and treatment with systemic anti-VEGF therapeutics</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">154</enrollment>
  <condition>Age - Related Macular Degeneration (AMD)</condition>
  <arm_group>
    <arm_group_label>Open label IAI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravitreal Aflibercept Injection (IAI)</intervention_name>
    <arm_group_label>Open label IAI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria include but are not limited to:&#xD;
&#xD;
          1. Men or women great than or equal to 50 years of age with unilateral neovascular AMD&#xD;
&#xD;
          2. BCVA ETDRS letter score of 73 to 24 (20/40 to 20/320) in the study eye&#xD;
&#xD;
          3. Active primary subfoveal choroidal neovascularization (CNV) lesions secondary to AMD,&#xD;
             including juxtafoveal lesions that affect the fovea as evidenced by FA in the study&#xD;
             eye&#xD;
&#xD;
          4. The CNV area must be at least 50% of total lesion size&#xD;
&#xD;
          5. Willing and able to comply with clinic visits and study-related procedures&#xD;
&#xD;
          6. Provide signed informed consent&#xD;
&#xD;
          7. Provide signed Health Insurance Portability and Accountability Act (HIPAA)&#xD;
             authorization&#xD;
&#xD;
        Exclusion criteria include but are not limited to:&#xD;
&#xD;
          1. Neovascular AMD in the fellow eye&#xD;
&#xD;
          2. Corneal endothelial measures as judged by an independent reading center&#xD;
&#xD;
          3. Any prior use of intraocular anti-VEGF treatment for neovascular AMD in either eye&#xD;
&#xD;
          4. Structural damage to the center of the macula in the study eye that is likely to&#xD;
             preclude improvement in BCVA following the resolution of macular edema&#xD;
&#xD;
          5. History of cataract surgery, or other intraocular surgery in either eye, within 1 year&#xD;
             of screening&#xD;
&#xD;
          6. History of cataract surgery, or other intraocular surgery in either eye, within 1 year&#xD;
             of screening, or yttrium aluminum garnet (YAG) Capsulotomy within 3 months of&#xD;
             screening&#xD;
&#xD;
          7. Contact lens wear in either eye within 6 months of screening&#xD;
&#xD;
          8. History of angle closure glaucoma in either eye&#xD;
&#xD;
          9. Intraocular laser therapy including selective laser trabeculoplasty (SLT), YAG,&#xD;
             prophylactic peripheral iridotomy (PI) in either eye within 1 year of screening, or&#xD;
             YAG Capsulotomy within 3 months of screening&#xD;
&#xD;
         10. History of cataract surgery requiring an anterior chamber intraocular lens implant at&#xD;
             any time in either eye&#xD;
&#xD;
         11. Any prior ocular trauma (blunt or penetrating) in either eye&#xD;
&#xD;
         12. Embedded corneal foreign body in either eye&#xD;
&#xD;
         13. Evidence of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either&#xD;
             eye&#xD;
&#xD;
         14. Ocular media of insufficient quality to obtain fundus and OCT images in the study eye&#xD;
&#xD;
         15. Any prior ocular inflammation/infection in either eye within 3 months of the screening&#xD;
             visit&#xD;
&#xD;
         16. Any prior use of amantadine&#xD;
&#xD;
         17. Significant pre-retinal fibrosis involving the macula in the study eye (where, in the&#xD;
             opinion of the investigator, the pre-retinal fibrosis is causing distortion or&#xD;
             traction on the central macular region which may be limiting vision, or inducing&#xD;
             retinal edema/thickening, beyond that due to underlying CNV)&#xD;
&#xD;
         18. Intraocular pressure (IOP) greater than or equal to 30 mm Hg in the study eye at&#xD;
             screening&#xD;
&#xD;
         19. Uncontrolled diabetes mellitus (DM) (HbA1c ≥8)&#xD;
&#xD;
         20. Current treatment with systemic anti-VEGF therapeutics at screening&#xD;
&#xD;
         21. Known serious allergy to the fluorescein sodium for injection in angiography&#xD;
&#xD;
         22. Participation in an investigational study within 30 days prior to the screening visit&#xD;
             that involved treatment with any drug (excluding vitamins and minerals) or device.&#xD;
&#xD;
         23. Positive serum hCG pregnancy test at the screening visit&#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>Clinical Trial Management</last_name>
    <role>Study Director</role>
    <affiliation>Regeneron Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Palm Desert</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Santa Ana</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Westlake Village</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Golden</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boynton Beach</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pensacola</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Plantation</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Winter Haven</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oak Park</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New Albany</city>
        <state>Indiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jackson</city>
        <state>Michigan</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Portsmouth</city>
        <state>New Hampshire</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bloomfield</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lawrenceville</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Northfield</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Teaneck</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Salem</city>
        <state>Oregon</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kingston</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Florence</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ladson</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>West Columbia</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rapid City</city>
        <state>South Dakota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Arlington</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>November 2, 2012</study_first_submitted>
  <study_first_submitted_qc>November 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <results_first_submitted>September 11, 2017</results_first_submitted>
  <results_first_submitted_qc>November 21, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 22, 2017</results_first_posted>
  <last_update_submitted>November 21, 2017</last_update_submitted>
  <last_update_submitted_qc>November 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>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>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 43 sites in the US from 14Nov2012 to 03Sep2015. The target study population consisted of men and women 50 years of age and older with neovascular AMD who met all study eligibility criteria. A total of 288 patients were screened, of whom 154 patients were enrolled and treated. A total of 126 patients completed week 100.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Open Label IAI</title>
          <description>2 mg IAI (Intravitreal Aflibercept Injection) at 4-week intervals (2Q4) up to week 8 for a total of 3 injections, and 2 mg at 8-week intervals (2Q8) thereafter until week 96</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="154"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="126"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Deviation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Relocation (did not wish to transfer)</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The baseline analysis population was based on the safety analysis set (SAF) and included all patients who received at least 1 dose of study drug, regardless of the treatment for the study eye or the fellow eye.</population>
      <group_list>
        <group group_id="B1">
          <title>Open Label IAI</title>
          <description>Intravitreal Aflibercept Injection (IAI)</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="154"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="154"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="137"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="154"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="96"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Best Corrected Visual Acuity (BCVA) in the study eye (Letters Read)</title>
          <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision.</description>
          <units>letters correctly read</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="154"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.3" spread="13.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Central Subfield Thickness in the study eye by Optical Coherence Tomography (OCT)</title>
          <description>Retinal and lesion characteristics (wet or dry) were evaluated using spectral domain OCT on the study eye and the fellow eye at every study visit.</description>
          <units>micrometers (μm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="154"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="420.5" spread="134.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Corneal Endothelial Cell Density - Endothelial Cell Density Evaluable Set (EES)</title>
          <description>Central ECD of the corneal endothelium in the study eye and the fellow eye was evaluated by specular microscopy.</description>
          <population>EES</population>
          <units>cells/mm^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Study eye</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2409.8" spread="363.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fellow eye</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2388.0" spread="383.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score From Baseline to Week 100 - Last Observation Carried Forward (LOCF)</title>
        <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. LOCF approach was used if any ETDRS letter score was missed after start of treatment, but baseline data were not carried forward. No formal statistical analyses were performed.</description>
        <time_frame>Baseline to Week 100</time_frame>
        <population>Results are presented for the full analysis set (FAS). FAS included all patients who received at least one dose of study drug in the study eye, had baseline Best Corrected Visual Acuity (BCVA) assessment on the study eye, and had at least one post-baseline BCVA assessment on the study eye.</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label IAI</title>
            <description>2 mg IAI (Intravitreal Aflibercept Injection) at 4-week intervals (2Q4) up to week 8 for a total of 3 injections, and 2 mg at 8-week intervals (2Q8) thereafter until week 96</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score From Baseline to Week 100 - Last Observation Carried Forward (LOCF)</title>
          <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. LOCF approach was used if any ETDRS letter score was missed after start of treatment, but baseline data were not carried forward. No formal statistical analyses were performed.</description>
          <population>Results are presented for the full analysis set (FAS). FAS included all patients who received at least one dose of study drug in the study eye, had baseline Best Corrected Visual Acuity (BCVA) assessment on the study eye, and had at least one post-baseline BCVA assessment on the study eye.</population>
          <units>letters correctly read</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="151"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.7" spread="20.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Week 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" spread="17.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Whose Optical Coherence Tomography (OCT) Status Was &quot;Dry&quot; at Week 52 and at Week 100 (LOCF)</title>
        <description>Retinal fluid status was evaluated using spectral domain OCT on the study eye at every study visit. Last observation carried forward (LOCF) method was used to impute missing data.</description>
        <time_frame>Baseline to Week 100</time_frame>
        <population>Full analysis set (FAS)</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label IAI</title>
            <description>2 mg IAI (Intravitreal Aflibercept Injection) at 4-week intervals (2Q4) up to week 8 for a total of 3 injections, and 2 mg at 8-week intervals (2Q8) thereafter until week 96</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Whose Optical Coherence Tomography (OCT) Status Was &quot;Dry&quot; at Week 52 and at Week 100 (LOCF)</title>
          <description>Retinal fluid status was evaluated using spectral domain OCT on the study eye at every study visit. Last observation carried forward (LOCF) method was used to impute missing data.</description>
          <population>Full analysis set (FAS)</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="151"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline: Dry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline: Not Dry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52: Dry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52: Not Dry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 100: Dry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 100: Not Dry</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Gained ≥15 ETDRS Letters Compared With Baseline at Week 52 and Week 100 (LOCF)</title>
        <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. LOCF approach was used if any ETDRS letter score was missed after start of treatment, but baseline data were not carried forward. No formal statistical analyses were performed.</description>
        <time_frame>At week 52 and At week 100</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label IAI</title>
            <description>2 mg IAI (Intravitreal Aflibercept Injection) at 4-week intervals (2Q4) up to week 8 for a total of 3 injections, and 2 mg at 8-week intervals (2Q8) thereafter until week 96</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Gained ≥15 ETDRS Letters Compared With Baseline at Week 52 and Week 100 (LOCF)</title>
          <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. LOCF approach was used if any ETDRS letter score was missed after start of treatment, but baseline data were not carried forward. No formal statistical analyses were performed.</description>
          <population>FAS</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="151"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At week 52</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>At week 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Best Corrected Visual Acuity Score Through Week 52 (LOCF)</title>
        <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision.</description>
        <time_frame>Baseline to Week 52</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label IAI</title>
            <description>2 mg IAI (Intravitreal Aflibercept Injection) at 4-week intervals (2Q4) up to week 8 for a total of 3 injections, and 2 mg at 8-week intervals (2Q8) thereafter until week 96</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Best Corrected Visual Acuity Score Through Week 52 (LOCF)</title>
          <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision.</description>
          <population>FAS</population>
          <units>Letters correctly read</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="151"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At Week 52</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.1" spread="18.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Week 52</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9" spread="15.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Gained ≥0, ≥5, ≥10, or ≥30 Letters From Baseline in BCVA Through Week 100 (LOCF)</title>
        <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.</description>
        <time_frame>Baseline to Week 100</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label IAI</title>
            <description>2 mg IAI (Intravitreal Aflibercept Injection) at 4-week intervals (2Q4) up to week 8 for a total of 3 injections, and 2 mg at 8-week intervals (2Q8) thereafter until week 96</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Gained ≥0, ≥5, ≥10, or ≥30 Letters From Baseline in BCVA Through Week 100 (LOCF)</title>
          <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.</description>
          <population>FAS</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="151"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Gained ≥ 0 Letters at Week 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gained ≥ 5 Letters at Week 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gained ≥10 Letters at Week 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gained ≥30 Letters at Week 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients Who Lost &gt;0, ≥5, ≥10, or ≥15 Letters From Baseline in BCVA Through Week 100 (LOCF)</title>
        <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.</description>
        <time_frame>Baseline to Week 100</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label IAI</title>
            <description>2 mg IAI (Intravitreal Aflibercept Injection) at 4-week intervals (2Q4) up to week 8 for a total of 3 injections, and 2 mg at 8-week intervals (2Q8) thereafter until week 96</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Who Lost &gt;0, ≥5, ≥10, or ≥15 Letters From Baseline in BCVA Through Week 100 (LOCF)</title>
          <description>Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.</description>
          <population>FAS</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="151"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Lost &gt;0 Letters at Week 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lost ≥5 Letters at Week 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lost ≥10 Letters at Week 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lost ≥15 Letters at Week 100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percent Change From Baseline in Corneal Endothelial Cell Density (ECD) at Week 24 and Week 52 in the Study Eye and the Fellow Eye - Endothelial Cell Density Evaluable Set (EES)</title>
        <description>EES included all eligible patients who were treated in the study eye, untreated in the fellow eye, had baseline specular microscopy image in both eyes, and completed week 52 evaluation in both eyes and treatment with systemic anti-VEGF therapeutics</description>
        <time_frame>At week 24 and At week 52</time_frame>
        <population>EES</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label IAI</title>
            <description>2 mg IAI (Intravitreal Aflibercept Injection) at 4-week intervals (2Q4) up to week 8 for a total of 3 injections, and 2 mg at 8-week intervals (2Q8) thereafter until week 96</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Corneal Endothelial Cell Density (ECD) at Week 24 and Week 52 in the Study Eye and the Fellow Eye - Endothelial Cell Density Evaluable Set (EES)</title>
          <description>EES included all eligible patients who were treated in the study eye, untreated in the fellow eye, had baseline specular microscopy image in both eyes, and completed week 52 evaluation in both eyes and treatment with systemic anti-VEGF therapeutics</description>
          <population>EES</population>
          <units>percent change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="118"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 24: Study eye</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="4.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24: Fellow eye</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="4.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52: Study eye</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2" spread="4.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52: Fellow eye</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="118"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="4.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected during the period baseline to week 100</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Open Label IAI</title>
          <description>2 mg IAI (Intravitreal Aflibercept Injection) at 4-week intervals (2Q4) up to week 8 for a total of 3 injections, and 2 mg at 8-week intervals (2Q8) thereafter until week 96</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 18.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Autoimmune haemolytic anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Coronary artery occlusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <description>Study eye</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Detachment of retinal pigment epithelium</sub_title>
                <description>Study eye</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Retinal haemorrhage</sub_title>
                <description>Study eye</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Retinal pigment epithelial tear</sub_title>
                <description>Study eye</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Diverticular perforation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Diverticulum</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Diverticulum intestinal haemorrhagic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Endophthalmitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Endophthalmitis</sub_title>
                <description>Study eye</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Gastroenteritis bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Perirectal abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Peritonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Fractured sacrum</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Pubis fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Cervical spinal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Osteonecrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Rheumatoid arthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Rotator cuff syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Bladder transitional cell carcinoma metastatic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Colon cancer metastatic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Plasma cell myeloma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of skin</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Transitional cell carcinoma metastatic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Carotid artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Embolic stroke</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Generalised tonic-clonic seizure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Lacunar infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Renal artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic aneurysm rupture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Thromboangiitis obliterans</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 18.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="38" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctival haemorrhage</sub_title>
                <description>Study eye</description>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Neovascular age-related macular degeneration</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Vitreous detachment</sub_title>
                <description>Study eye</description>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Vitreous floaters</sub_title>
                <description>Study eye</description>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="154"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="154"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>After completion of the trial, the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review; provided that the sponsor can remove confidential or proprietary information from such communications. The sponsor cannot require other changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Trial Administrator</name_or_title>
      <organization>Regeneron Pharmaceuticals, Inc.</organization>
      <email>clinicaltrials@regeneron.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01722045
org study id: VGFTe-AMD-1124
nct id: NCT01722045
lead sponsor: 
has dmc: No
This is a phase 4, open-label, single arm, multicenter, clinical study in patients with
      neovascular AMD designed to evaluate the efficacy and safety of Intravitreal Aflibercept
      Injection (IAI) administered over 2 years , and to provide clinical information from the
      first year in the trial evaluating the adverse effects, if any, on the corneal endothelium
      following administration of IAI.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score From Baseline to Week 100 - Last Observation Carried Forward (LOCF)
time frame: Baseline to Week 100
description: Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. LOCF approach was used if any ETDRS letter score was missed after start of treatment, but baseline data were not carried forward. No formal statistical analyses were performed.
measure: Percentage of Participants Whose Optical Coherence Tomography (OCT) Status Was "Dry" at Week 52 and at Week 100 (LOCF)
time frame: Baseline to Week 100
description: Retinal fluid status was evaluated using spectral domain OCT on the study eye at every study visit. Last observation carried forward (LOCF) method was used to impute missing data.
measure: Percentage of Participants Who Gained ≥15 ETDRS Letters Compared With Baseline at Week 52 and Week 100 (LOCF)
time frame: At week 52 and At week 100
description: Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision. LOCF approach was used if any ETDRS letter score was missed after start of treatment, but baseline data were not carried forward. No formal statistical analyses were performed.
measure: Change From Baseline in Best Corrected Visual Acuity Score Through Week 52 (LOCF)
time frame: Baseline to Week 52
description: Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better vision.
measure: Percentage of Participants Who Gained ≥0, ≥5, ≥10, or ≥30 Letters From Baseline in BCVA Through Week 100 (LOCF)
time frame: Baseline to Week 100
description: Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.
measure: Percentage of Patients Who Lost >0, ≥5, ≥10, or ≥15 Letters From Baseline in BCVA Through Week 100 (LOCF)
time frame: Baseline to Week 100
description: Visual function of the study eye was assessed at a distance of 4 meters at every study visit using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning.
measure: Percent Change From Baseline in Corneal Endothelial Cell Density (ECD) at Week 24 and Week 52 in the Study Eye and the Fellow Eye - Endothelial Cell Density Evaluable Set (EES)
time frame: At week 24 and At week 52
description: EES included all eligible patients who were treated in the study eye, untreated in the fellow eye, had baseline specular microscopy image in both eyes, and completed week 52 evaluation in both eyes and treatment with systemic anti-VEGF therapeutics
arm group label: Open label IAI
arm group type: Experimental
intervention type: Drug
intervention name: Intravitreal Aflibercept Injection (IAI)
arm group label: Open label IAI
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trial Management
role: Study Director
affiliation: Regeneron Pharmaceuticals
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country: United States
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: Aflibercept
participant flow: 
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