<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/NCT04423718</url>
  </required_header>
  <id_info>
    <org_study_id>20968</org_study_id>
    <secondary_id>2019-003851-12</secondary_id>
    <nct_id>NCT04423718</nct_id>
  </id_info>
  <brief_title>Study to Gather Information on Safety and Use of High Dose Aflibercept Injection Into the Eye in Patients With an Age Related Eye Disorder That Causes Blurred Vision or a Blind Spot Due to Abnormal Blood Vessels That Leak Fluid Into the Light Sensitive Lining Inside the Eye</brief_title>
  <acronym>PULSAR</acronym>
  <official_title>Randomized, Double-Masked, Active-Controlled, Phase 3 Study of the Efficacy and Safety of High Dose Aflibercept in Patients With Neovascular Age-Related Macular Degeneration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Bayer</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study researchers want to learn more about changes in visual acuity (clarity of&#xD;
      vision) with a high dose treatment with Aflibercept (Eylea) in patients suffering from&#xD;
      neovascular age-related macular degeneration (nAMD). Neovascular AMD is an eye disease that&#xD;
      causes blurred vision or a blind spot due to abnormal blood vessels that leak fluid or blood&#xD;
      into the light sensitive lining inside the eye (retina). The fluid buildup causes the central&#xD;
      part of the retina (macula) responsible for sharp, straight-ahead vision to swell and thicken&#xD;
      (edema), which distorts vision.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 11, 2020</start_date>
  <completion_date type="Anticipated">August 12, 2024</completion_date>
  <primary_completion_date type="Actual">July 18, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Up to Week 108: Participant and Investigator masked. Week 108 to Week 156: Participant and Investigator unmasked to treatment intervals.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48</measure>
    <time_frame>At baseline and Week 48</time_frame>
    <description>Visual function of the study eye was assessed at a distance of 4 meters using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60</measure>
    <time_frame>At baseline and Week 60</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16</measure>
    <time_frame>At Week 16</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48</measure>
    <time_frame>At baseline and Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48</measure>
    <time_frame>At Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48</measure>
    <time_frame>At baseline and Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Total Lesion Area From Baseline to Week 48</measure>
    <time_frame>At baseline and Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48</measure>
    <time_frame>At Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48</measure>
    <time_frame>At baseline and Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48</measure>
    <time_frame>At baseline and Week 48</time_frame>
    <description>NEI VFQ-25 was a 25-item questionnaire that gave a score on a scale from 0 (worst) to 100 (best = no vision problems)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)</measure>
    <time_frame>Up to 156 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48</measure>
    <time_frame>Up to Week 48</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through End of Masked Study</measure>
    <time_frame>Up to week 96</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">1011</enrollment>
  <condition>Neovascular Age-Related Macular Degeneration</condition>
  <arm_group>
    <arm_group_label>Aflibercept 2q8</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In the double-masked study part (Years 1 and 2), Aflibercept 2 mg administered every 8 weeks after a loading phase. (Active Comparator) In Year 3, high dose aflibercept administered according to individual patient response. (Experimental)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aflibercept HDq12</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aflibercept high dose (HD) administered every 12 weeks after an initiation phase. Treatment intervals adjusted according to individual patient response.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aflibercept HDq16</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aflibercept high dose administered every 16 weeks after an initiation phase. Treatment intervals adjusted according to individual patient response.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)</intervention_name>
    <description>Solution in Vial, intravitreal (IVT) injection</description>
    <arm_group_label>Aflibercept 2q8</arm_group_label>
    <arm_group_label>Aflibercept HDq12</arm_group_label>
    <arm_group_label>Aflibercept HDq16</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept VEGF Trap-Eye (Eylea, BAY86-5321)</intervention_name>
    <description>Solution in Vial, 2 mg, intravitreal (IVT) injection</description>
    <arm_group_label>Aflibercept 2q8</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Active subfoveal CNV secondary to nAMD, including juxtafoveal lesions that affect the&#xD;
             fovea as assessed in the study eye.&#xD;
&#xD;
          -  Total area of CNV (including both classic and occult components) must comprise greater&#xD;
             than 50% of the total lesion area in the study eye.&#xD;
&#xD;
          -  BCVA ETDRS letter score of 78 to 24 (corresponding to a Snellen equivalent of&#xD;
             approximately 20/32 to 20/320) in the study eye.&#xD;
&#xD;
          -  Decrease in BCVA determined to be primarily the result of nAMD in the study eye.&#xD;
&#xD;
          -  Presence of IRF and/or SRF affecting the central subfield of the study eye on OCT.&#xD;
&#xD;
          -  Contraceptive use by men or women should be consistent with local regulations&#xD;
             regarding the methods of highly effective contraception for those participating in&#xD;
             clinical studies.&#xD;
&#xD;
          -  Other protocol-specified inclusion criteria.&#xD;
&#xD;
        Additional inclusion criteria for Year 3:&#xD;
&#xD;
          -  At least one BCVA value and one central subfield retinal thickness (CST) value from&#xD;
             measurements at one of the following visits: Visit 24 (Week 84), Visit 25 (Week 88) or&#xD;
             Visit 26 (Week 92).&#xD;
&#xD;
          -  Participant is enrolled at a site that participates in the extension period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Causes of CNV other than nAMD in the study eye.&#xD;
&#xD;
          -  Scar, fibrosis, or atrophy involving the central subfield in the study eye.&#xD;
&#xD;
          -  Presence of retinal pigment epithelial tears or rips involving the central subfield in&#xD;
             the study eye.&#xD;
&#xD;
          -  Uncontrolled glaucoma (defined as IOP &gt;25 mmHg despite treatment with anti-glaucoma&#xD;
             medication) in the study eye.&#xD;
&#xD;
          -  History of idiopathic or autoimmune uveitis in the study eye.&#xD;
&#xD;
          -  Myopia of a spherical equivalent of at least 8 diopters in the study eye prior to any&#xD;
             refractive or cataract surgery.&#xD;
&#xD;
          -  History or clinical evidence of diabetic retinopathy, diabetic macular edema, or any&#xD;
             retinal vascular disease other than nAMD in either eye.&#xD;
&#xD;
          -  Evidence of extraocular or periocular infection or inflammation (including infectious&#xD;
             blepharitis, keratitis, scleritis, or conjunctivitis) in either eye at the time of&#xD;
             screening/randomization.&#xD;
&#xD;
          -  Uncontrolled blood pressure (defined as systolic &gt;160 mmHg or diastolic &gt;95 mmHg).&#xD;
&#xD;
          -  Any prior or concomitant ocular (in the study eye) or systemic treatment (with an&#xD;
             investigational or approved, anti-VEGF or other agent) or surgery for nAMD, except&#xD;
             dietary supplements or vitamins.&#xD;
&#xD;
          -  Other protocol-specified exclusion criteria&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Arizona Retina and Vitreous Consultants - Research</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Orange County</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093-0698</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northern California Retina-Vitreous Associates</name>
      <address>
        <city>Mountain View</city>
        <state>California</state>
        <zip>94040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Eye Specialists</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants San Diego</name>
      <address>
        <city>Poway</city>
        <state>California</state>
        <zip>92064-2526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Southern California</name>
      <address>
        <city>Redlands</city>
        <state>California</state>
        <zip>92374</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Riverside Medical Center</name>
      <address>
        <city>Riverside</city>
        <state>California</state>
        <zip>92505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Southern Colorado, PC</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New England Retina Associates</name>
      <address>
        <city>New London</city>
        <state>Connecticut</state>
        <zip>06320</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rand Eye Institute</name>
      <address>
        <city>Deerfield Beach</city>
        <state>Florida</state>
        <zip>33064</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Group of Florida</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vitreo-Retinal Associates</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Retina Institute</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Eye Associates</name>
      <address>
        <city>Melbourne</city>
        <state>Florida</state>
        <zip>32901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Macula Specialists of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33126</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Retina Institute</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Specialists</name>
      <address>
        <city>Pensacola</city>
        <state>Florida</state>
        <zip>32503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Vitreous Associates of Florida - Saint Petersburg</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33711-1141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Vitreoretinal Associates</name>
      <address>
        <city>Tallahassee</city>
        <state>Florida</state>
        <zip>32308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Hawaii</name>
      <address>
        <city>'Aiea</city>
        <state>Hawaii</state>
        <zip>96701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Associates IL</name>
      <address>
        <city>Elmhurst</city>
        <state>Illinois</state>
        <zip>60126</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Retina and Macula Associates</name>
      <address>
        <city>Oak Forest</city>
        <state>Illinois</state>
        <zip>60452</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wolfe Eye Clinic, PC</name>
      <address>
        <city>West Des Moines</city>
        <state>Iowa</state>
        <zip>50266</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Care Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ophthalmic Consultants of Boston</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vitreo Retinal Surgery PA</name>
      <address>
        <city>Edina</city>
        <state>Minnesota</state>
        <zip>55435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Center of New Jersey</name>
      <address>
        <city>Bloomfield</city>
        <state>New Jersey</state>
        <zip>07003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NJ Retina</name>
      <address>
        <city>Edison</city>
        <state>New Jersey</state>
        <zip>08820</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eye Associates of New Mexico</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87109-5853</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Long Island Vitreoretinal Consultants</name>
      <address>
        <city>Great Neck</city>
        <state>New York</state>
        <zip>11021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Long Island Vitreoretinal Consultants</name>
      <address>
        <city>Hauppauge</city>
        <state>New York</state>
        <zip>11788</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ophthalmic Consultants of Long Island</name>
      <address>
        <city>Lynbrook</city>
        <state>New York</state>
        <zip>11563</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ophthalmic Consultants of the Capital Region</name>
      <address>
        <city>Troy</city>
        <state>New York</state>
        <zip>12180</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest Baptist Health</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157-1045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Midwest Retina - Main Office</name>
      <address>
        <city>Dublin</city>
        <state>Ohio</state>
        <zip>43016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Northwest, PC</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants, LLC</name>
      <address>
        <city>Salem</city>
        <state>Oregon</state>
        <zip>97302-2152</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mid Atlantic Retina</name>
      <address>
        <city>Bethlehem</city>
        <state>Pennsylvania</state>
        <zip>18017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erie Retinal Surgery, Inc.</name>
      <address>
        <city>Erie</city>
        <state>Pennsylvania</state>
        <zip>16507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eye Care Specialists</name>
      <address>
        <city>Kingston</city>
        <state>Pennsylvania</state>
        <zip>18704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charleston Neuroscience Center</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Palmetto Retina Center, LLC</name>
      <address>
        <city>West Columbia</city>
        <state>South Carolina</state>
        <zip>29169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Black Hills Regional Eye Institute</name>
      <address>
        <city>Rapid City</city>
        <state>South Dakota</state>
        <zip>57701-7374</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charles Retina Institute</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical School</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Retina Associates</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Retina Associates</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center Ophthalmology Associates</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retinal Consultants of Texas - San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Houston</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77384</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Texas - The Woodlands</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77384</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fletcher Allen Health Care</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05401-1420</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spokane Eye Clinical Research</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Virginia University</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin - Madison</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Organizacion Medica de Investigacion (OMI)</name>
      <address>
        <city>Buenos Aires</city>
        <state>Ciudad Auton. De Buenos Aires</state>
        <zip>C1015ABO</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OFTALMOS, Instituto Oftalmologico de Alta Complejidad</name>
      <address>
        <city>Buenos Aires</city>
        <state>Ciudad Auton. De Buenos Aires</state>
        <zip>C1120AAN</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eyeclinic Albury Wodonga</name>
      <address>
        <city>Albury</city>
        <state>New South Wales</state>
        <zip>2640</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sydney Retina Clinic</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westmead Hospital</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hobart Eye Surgeons</name>
      <address>
        <city>Hobart</city>
        <state>Tasmania</state>
        <zip>7000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marsden Eye Surgery Center</name>
      <address>
        <city>Parramatta</city>
        <zip>2150</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Klagenfurt am Wörthersee</name>
      <address>
        <city>Klagenfurt</city>
        <state>Kärnten</state>
        <zip>9020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kepler Universitätsklinikum Campus III</name>
      <address>
        <city>Linz</city>
        <state>Oberösterreich</state>
        <zip>4020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Konventhospital Barmherzige Brüder Linz</name>
      <address>
        <city>Linz</city>
        <state>Oberösterreich</state>
        <zip>4021</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Universität Graz</name>
      <address>
        <city>Graz</city>
        <state>Steiermark</state>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hanusch-Krankenhaus Wien</name>
      <address>
        <city>Wien</city>
        <zip>1140</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SEHAT Pentagram</name>
      <address>
        <city>Sofia</city>
        <zip>1309</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spec. Hosp. for Active Treatment for Eye Diseases Zrenie</name>
      <address>
        <city>Sofia</city>
        <zip>1408</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMHAT Alexandrovska EAD</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multiprofile Hospital for Active Treatment Sveta Sofia</name>
      <address>
        <city>Sofia</city>
        <zip>1618</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Specialized Hospital For Active Treatment of Eye Diseases Zora</name>
      <address>
        <city>Sofia</city>
        <zip>1784</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sveta Petka Eye Hospital</name>
      <address>
        <city>Varna</city>
        <zip>9002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St.Joseph's Health Care-London</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4V2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto Retina Institute</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M3C 0G9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de l'Oeil des Laurentides</name>
      <address>
        <city>Boisbriand</city>
        <state>Quebec</state>
        <zip>J7H1S6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Hospital of Anhui medical university</name>
      <address>
        <city>Hefei</city>
        <state>Anhui</state>
        <zip>230601</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The 1st Affiliated Hospital Fujian Medical University</name>
      <address>
        <city>Fuzhou</city>
        <state>Fujian</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guangzhou Aier Eye Hospital</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>634050</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shijiazhuang General Hospital</name>
      <address>
        <city>Shijiazhuang</city>
        <state>Hebei</state>
        <zip>050000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hebei Eye Hospital</name>
      <address>
        <city>Xingtai</city>
        <state>Hebei</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henan Provincial Ophthalmology Hospital (Henan Eye Institute</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <zip>450003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tongji Hosp. of Tongji Med Coll, Huazhong Uni of Sci &amp; Tech.</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430030</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Union Hospt Tongji Medical Colleg. Huazhong univ. Scien&amp;Tech</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430030</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First People's Hospital of Xuzhou</name>
      <address>
        <city>Xuzhou</city>
        <state>Jiangsu</state>
        <zip>221002</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jiangxi Provincial People's Hospital</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <zip>330006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of NanChang University</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <zip>330006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eye Center of the second Bethune Hospital, jinlin University</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <zip>130022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tonghua Central Hospital</name>
      <address>
        <city>Tonghua</city>
        <state>Jilin</state>
        <zip>134001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shenyang He Eye Hospital</name>
      <address>
        <city>Shenyang</city>
        <state>Liaoning</state>
        <zip>110034</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The People's Hospital of Ningxia Hui Autonomous Region</name>
      <address>
        <city>Yinchuan</city>
        <state>Ningxia</state>
        <zip>750000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Xi'an Jiaotong University</name>
      <address>
        <city>Xi'an</city>
        <state>Shanxi</state>
        <zip>710061</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aier Eye Hospital (Chengdu)</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Xinjiang Medical University</name>
      <address>
        <city>Urumqi</city>
        <state>Xinjiang</state>
        <zip>830054</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The 1st Affiliated Hospital of Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ZheJiang Provincial People's Hospital</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310014</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Affiliated Eye Hospital of Wenzhou Medical College</name>
      <address>
        <city>Wenzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing Tongren Hospital, Capital Medical University (East)</name>
      <address>
        <city>Beijing</city>
        <zip>100005</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing Aier Intech Eye Hospital Co. LTD - Ophthalmology</name>
      <address>
        <city>Beijing</city>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking University People's Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100044</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chongqing Aier Ophthalmology Hospital</name>
      <address>
        <city>Chongqing</city>
        <zip>400020</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Tongji Hospital of Tongji University</name>
      <address>
        <city>Shanghai</city>
        <zip>200065</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai General Hospital</name>
      <address>
        <city>Shanghai</city>
        <zip>200080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tianjin Medical University General Hospital</name>
      <address>
        <city>Tianjin</city>
        <zip>300052</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tianjin Medical University Eye Hospital</name>
      <address>
        <city>Tianjin</city>
        <zip>300384</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TianJin eye hospital</name>
      <address>
        <city>Tianjin</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni Nemocnice Hradec Kralove</name>
      <address>
        <city>Hradec Kralove</city>
        <zip>500 05</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Ostrava</name>
      <address>
        <city>Ostrava</city>
        <zip>708 52</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Plzen - Lochotin</name>
      <address>
        <city>Plzen-Lochotin</city>
        <zip>323 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charles University in Prague</name>
      <address>
        <city>Prague</city>
        <zip>110 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Kralovske Vinohrady</name>
      <address>
        <city>Praha 10</city>
        <zip>10034</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lexum a.s., Evropska ocni klinika</name>
      <address>
        <city>Praha 4</city>
        <zip>140 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AXON Clinical s.r.o.</name>
      <address>
        <city>Praha 5</city>
        <zip>150 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Tallinn Central Hospital</name>
      <address>
        <city>Tallinn</city>
        <zip>10138</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tartu University Hospital</name>
      <address>
        <city>Tartu</city>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre d'Ophtalmologie - Paradis-Monticelli</name>
      <address>
        <city>Marseille</city>
        <zip>13008</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Lariboisière - Paris</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre ophtalmologique Saint-Exupéry</name>
      <address>
        <city>Saint-Cyr-Sur-Loire</city>
        <zip>37540</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LTD &quot;Clinic LJ&quot;</name>
      <address>
        <city>Kutaisi</city>
        <zip>4600</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JSC &quot;Evex Hospitals'</name>
      <address>
        <city>Tbilisi</city>
        <zip>0186</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LTD &quot;Innova&quot;</name>
      <address>
        <city>Tbilisi</city>
        <zip>105</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LTD &quot;Chichua Medical Center MZERA&quot;</name>
      <address>
        <city>Tbilisi</city>
        <zip>114</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Budapest Retina Associates</name>
      <address>
        <city>Budapest</city>
        <zip>1133</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szent-Gyorgyi Albert Orvostudomanyi Egyetem</name>
      <address>
        <city>Szeged</city>
        <zip>6720</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Health Corporation</name>
      <address>
        <city>Haifa</city>
        <zip>3109601</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lady Davis Carmel Medical Center</name>
      <address>
        <city>Haifa</city>
        <zip>3436212</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Hebrew University Hospital Ein Kerem</name>
      <address>
        <city>Jerusalem</city>
        <zip>9112001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meir Medical Center</name>
      <address>
        <city>Kfar Saba</city>
        <zip>4428164</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chaim Sheba Medical Center</name>
      <address>
        <city>Ramat Gan</city>
        <zip>5262000</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaplan Medical Center</name>
      <address>
        <city>Rehovot</city>
        <zip>7610001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Assuta Medical Centers - HaShalom</name>
      <address>
        <city>Tel Aviv</city>
        <zip>6789140</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione PTV Policlinico Tor Vergata</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Fondazione G.B. Bietti Studio e Ricerca in Otalmologia</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00198</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Raffaele s.r.l.</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ASST Fatebenefratelli Sacco</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20157</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U. di Cagliari</name>
      <address>
        <city>Cagliari</city>
        <state>Sardegna</state>
        <zip>09124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. di Perugia</name>
      <address>
        <city>Perugia</city>
        <state>Umbria</state>
        <zip>06129</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Daiyukai Daiichi Hospital</name>
      <address>
        <city>Ichinomiya</city>
        <state>Aichi</state>
        <zip>491-8551</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aichi Medical University Hospital</name>
      <address>
        <city>Nagakute</city>
        <state>Aichi</state>
        <zip>480-1195</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nagoya University Hospital</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <zip>466-8560</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nagoya City University Hospital</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <zip>467-8602</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kokura Memorial Hospital</name>
      <address>
        <city>Kitakyushu</city>
        <state>Fukuoka</state>
        <zip>802-8555</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kurume University Hospital</name>
      <address>
        <city>Kurume</city>
        <state>Fukuoka</state>
        <zip>830-0011</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Tohoku Eye Clinic</name>
      <address>
        <city>Koriyama</city>
        <state>Fukushima</state>
        <zip>963-8052</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gunma University Hospital</name>
      <address>
        <city>Maebashi</city>
        <state>Gunma</state>
        <zip>371-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sapporo City General Hospital</name>
      <address>
        <city>Sapporo</city>
        <state>Hokkaido</state>
        <zip>060-8604</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>KKR Sapporo Medical Center</name>
      <address>
        <city>Sapporo</city>
        <state>Hokkaido</state>
        <zip>062-0931</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hyogo Prefectural Amagasaki General Medical Center</name>
      <address>
        <city>Amagasaki</city>
        <state>Hyogo</state>
        <zip>660-8550</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kobe University Hospital</name>
      <address>
        <city>Kobe</city>
        <state>Hyogo</state>
        <zip>650-0017</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kozawa Eye Hospital and Diabetes Center</name>
      <address>
        <city>Mito</city>
        <state>Ibaraki</state>
        <zip>310-0845</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kanazawa Medical University Hospital</name>
      <address>
        <city>Kahoku-gun</city>
        <state>Ishikawa</state>
        <zip>920-0293</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kanazawa University Hospital</name>
      <address>
        <city>Kanazawa</city>
        <state>Ishikawa</state>
        <zip>920-8641</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kagawa University Hospital</name>
      <address>
        <city>Kita-gun</city>
        <state>Kagawa</state>
        <zip>761-0793</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical corporation Eiwakai Dannoue Ophthalmology clinic</name>
      <address>
        <city>Kawasaki</city>
        <state>Kanagawa</state>
        <zip>211-0053</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Marianna University Hospital</name>
      <address>
        <city>Kawasaki</city>
        <state>Kanagawa</state>
        <zip>216-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Otakeganka Tsukimino Clinic</name>
      <address>
        <city>Yamato</city>
        <state>Kanagawa</state>
        <zip>242-0001</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mie University Hospital</name>
      <address>
        <city>Tsu</city>
        <state>Mie</state>
        <zip>514-8507</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shinshu University Hospital</name>
      <address>
        <city>Matsumoto</city>
        <state>Nagano</state>
        <zip>390-8621</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nara Medical University Hospital</name>
      <address>
        <city>Kashihara</city>
        <state>Nara</state>
        <zip>634-8522</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oita University Hospital</name>
      <address>
        <city>Yufu</city>
        <state>Oita</state>
        <zip>879-5593</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kurashiki Medical Center</name>
      <address>
        <city>Kurashiki</city>
        <state>Okayama</state>
        <zip>710-8522</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of the Ryukyus Hospital</name>
      <address>
        <city>Nakagami</city>
        <state>Okinawa</state>
        <zip>903-0215</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kansai Medical University Hospital</name>
      <address>
        <city>Hirakata</city>
        <state>Osaka</state>
        <zip>573-1191</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kansai Medical University Medical Center</name>
      <address>
        <city>Moriguchi</city>
        <state>Osaka</state>
        <zip>570-8507</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kindai University Hospital</name>
      <address>
        <city>Osakasayama</city>
        <state>Osaka</state>
        <zip>589-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Tokyo Hospital</name>
      <address>
        <city>Bunkyo-ku</city>
        <state>Tokyo</state>
        <zip>113-8655</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St.Luke's International Hospital</name>
      <address>
        <city>Chuoku</city>
        <state>Tokyo</state>
        <zip>104-8560</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nishikasai Inouye Eye Hospital</name>
      <address>
        <city>Edogawa-ku</city>
        <state>Tokyo</state>
        <zip>134-0088</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokyo Medical University Hachioji Medical Center</name>
      <address>
        <city>Hachioji</city>
        <state>Tokyo</state>
        <zip>193-0998</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokiwadai Muranaka Eye Clinic</name>
      <address>
        <city>Itabashi-ku</city>
        <state>Tokyo</state>
        <zip>174-0071</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Tokyo Medical Center</name>
      <address>
        <city>Meguro-ku</city>
        <state>Tokyo</state>
        <zip>152-8902</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Keio University Hospital</name>
      <address>
        <city>Shinjuku-ku</city>
        <state>Tokyo</state>
        <zip>160-8582</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokyo Women's Medical University Hospital</name>
      <address>
        <city>Shinjuku-ku</city>
        <state>Tokyo</state>
        <zip>162-8666</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yamaguchi University Hospital</name>
      <address>
        <city>Ube</city>
        <state>Yamaguchi</state>
        <zip>755-8505</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Yamanashi Hospital</name>
      <address>
        <city>Chuo</city>
        <state>Yamanashi</state>
        <zip>409-3898</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akita University Hospital</name>
      <address>
        <city>Akita</city>
        <zip>010-8543</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hayashi Eye Hospital</name>
      <address>
        <city>Fukuoka</city>
        <zip>812-0011</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fukushima Medical University Hospital</name>
      <address>
        <city>Fukushima</city>
        <zip>960-1295</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hiroshima University Hospital</name>
      <address>
        <city>Hiroshima</city>
        <zip>734-8551</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miyazaki Hospital</name>
      <address>
        <city>Miyazaki</city>
        <zip>889-1692</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Japanese Red Cross Nagasaki Genbaku Hospital</name>
      <address>
        <city>Nagasaki</city>
        <zip>852-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Okayama University Hospital</name>
      <address>
        <city>Okayama</city>
        <zip>700-8558</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Japanese Red Cross Saitama Hospital</name>
      <address>
        <city>Saitama</city>
        <zip>330-8553</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokushima University Hospital</name>
      <address>
        <city>Tokushima</city>
        <zip>770-8503</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Japanese Red Cross Wakayama Medical center</name>
      <address>
        <city>Wakayama</city>
        <zip>640-8558</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yamagata University Hospital</name>
      <address>
        <city>Yamagata</city>
        <zip>990-9585</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam-si</city>
        <state>Gyeonggido</state>
        <zip>13620</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pusan National University Hospital</name>
      <address>
        <city>Busan</city>
        <zip>49241</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inje University Haeundae Paik Hospital</name>
      <address>
        <city>Busan</city>
        <zip>612-862</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Center Nune Eye Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>135-280</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Ophthalmology</name>
      <address>
        <city>Riga</city>
        <zip>1002</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riga East Clinical University Hospital &quot;Gailezers&quot;</name>
      <address>
        <city>Riga</city>
        <zip>LV-1006</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Latvian American Eye Center</name>
      <address>
        <city>Riga</city>
        <zip>LV-1009</zip>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital of LT University of Health Sciences Kaunas Clinics</name>
      <address>
        <city>Kaunas</city>
        <zip>LT-50161</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PI Klaipedos University Hospital</name>
      <address>
        <city>Klaipeda</city>
        <zip>LT-92288</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vilnius University Hospital Santaros Klinikos</name>
      <address>
        <city>Vilnius</city>
        <zip>LT-08661</zip>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ALM Oftalmolaser - Oftalmologia Medica e Cirurgica</name>
      <address>
        <city>Lisbon</city>
        <state>Lisboa</state>
        <zip>1050-078</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AIBILI</name>
      <address>
        <city>Coimbra</city>
        <zip>3000-548</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Espaco Medico de Coimbra</name>
      <address>
        <city>Coimbra</city>
        <zip>3000-548</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar Universitario do Porto</name>
      <address>
        <city>Porto</city>
        <zip>4099-001</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar Vila Nova de Gaia/Espinho | Unit 1 - Clinical Research Office</name>
      <address>
        <city>Porto</city>
        <zip>4434-502</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scientific Research Institution of Ophthalmic Diseases</name>
      <address>
        <city>Moscow</city>
        <zip>119021</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FBSI IRTC Eye Microsurgery n.a. acad. S.N. Fyodorov</name>
      <address>
        <city>Moscow</city>
        <zip>127486</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center of Serbia</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical hospital center Zvezdara</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinicki centar Vojvodine</name>
      <address>
        <city>Novi Sad</city>
        <zip>21000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>119074</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Singapore National Eye Centre</name>
      <address>
        <city>Singapore</city>
        <zip>168751</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultna nemocnica Nitra</name>
      <address>
        <city>Nitra</city>
        <zip>950 01</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemocnica s Poliklinikou Trebisov, Svet zdravia a.s.</name>
      <address>
        <city>Trebisov</city>
        <zip>075 01</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultna nemocnica Trencin</name>
      <address>
        <city>Trencin</city>
        <zip>911 71</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultna nemocnica s poliklinikou Zilina</name>
      <address>
        <city>Zilina</city>
        <zip>012 07</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Oftalmológico Francisco Gomez Ulla</name>
      <address>
        <city>Santiago de Compostela</city>
        <state>A Coruña</state>
        <zip>15706</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic i Provincial de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>8036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de la Santa Creu i Sant Pau | Gynecology Department</name>
      <address>
        <city>Barcelona</city>
        <zip>8041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Reina Sofía</name>
      <address>
        <city>Córdoba</city>
        <zip>14004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari i Politècnic La Fe</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RétinElysée</name>
      <address>
        <city>Lausanne</city>
        <state>Vaud</state>
        <zip>1006</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Berner Augenklinik am Lindenhofspital</name>
      <address>
        <city>Bern</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stadtspital Triemli</name>
      <address>
        <city>Zürich</city>
        <zip>8063</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shin Kong Wu Ho-Su Memorial Hospital</name>
      <address>
        <city>Taipei City</city>
        <state>Taipei</state>
        <zip>111</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital at Linkou</name>
      <address>
        <city>Taoyuan</city>
        <zip>33305</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Private enterprise private production company &quot; Acinus&quot;</name>
      <address>
        <city>Kropyvnytskyi</city>
        <zip>25006</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centralna Polyclinica MVS Ukraiiny</name>
      <address>
        <city>Kyiv</city>
        <zip>01024</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Poltava Regional Clinical Hospital n.a. M.V. Skliphosovskyi</name>
      <address>
        <city>Poltava</city>
        <zip>36011</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Austria</country>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>China</country>
    <country>Czechia</country>
    <country>Estonia</country>
    <country>France</country>
    <country>Georgia</country>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Latvia</country>
    <country>Lithuania</country>
    <country>Portugal</country>
    <country>Russian Federation</country>
    <country>Serbia</country>
    <country>Singapore</country>
    <country>Slovakia</country>
    <country>Spain</country>
    <country>Switzerland</country>
    <country>Taiwan</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Belgium</country>
    <country>Colombia</country>
    <country>Denmark</country>
    <country>Germany</country>
    <country>Hong Kong</country>
    <country>Netherlands</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
  </removed_countries>
  <link>
    <url>https://clinicaltrials.bayer.com/</url>
    <description>Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <results_first_submitted>July 9, 2023</results_first_submitted>
  <results_first_submitted_qc>August 11, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">September 6, 2023</results_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>nAMD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Degeneration</mesh_term>
    <mesh_term>Wet Macular Degeneration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aflibercept</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA &quot;Principles for responsible clinical trial data sharing&quot;. This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.&#xD;
Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 27, 2023</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT04423718/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 22, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT04423718/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 251 centers in 27 countries/regoins with first participant first visit on 20-AUG-2020 and primary completion on 18-JUL-2022. The study is still ongoing.</recruitment_details>
      <pre_assignment_details>Overall, 1395 participants were screened, of whom 383 participants did not complete screening, 1 participant was randomized in error although he/she did not complete screening and had withdrawn consent. A total of 1011 participants were randomized in nearly equal numbers to 1 of the 3 treatment groups.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Aflibercept 2q8</title>
          <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals</description>
        </group>
        <group group_id="P2">
          <title>Aflibercept HDq12</title>
          <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
        </group>
        <group group_id="P3">
          <title>Aflibercept HDq16</title>
          <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="337"/>
                <participants group_id="P2" count="336"/>
                <participants group_id="P3" count="338"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="336"/>
                <participants group_id="P2" count="335"/>
                <participants group_id="P3" count="338"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="309"/>
                <participants group_id="P2" count="316"/>
                <participants group_id="P3" count="312"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="26"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>COVID-19 pandemic</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Unknown if completed study until Week 48</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full analysis set: included all participants who had been randomly assigned to study treatment and who received at least 1 dose of study treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Aflibercept 2q8</title>
          <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals</description>
        </group>
        <group group_id="B2">
          <title>Aflibercept HDq12</title>
          <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
        </group>
        <group group_id="B3">
          <title>Aflibercept HDq16</title>
          <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="336"/>
            <count group_id="B2" value="335"/>
            <count group_id="B3" value="338"/>
            <count group_id="B4" value="1009"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</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="336"/>
                    <count group_id="B2" value="335"/>
                    <count group_id="B3" value="338"/>
                    <count group_id="B4" value="1009"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74.2" spread="8.8"/>
                    <measurement group_id="B2" value="74.7" spread="7.9"/>
                    <measurement group_id="B3" value="74.5" spread="8.5"/>
                    <measurement group_id="B4" value="74.5" spread="8.4"/>
                  </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="336"/>
                    <count group_id="B2" value="335"/>
                    <count group_id="B3" value="338"/>
                    <count group_id="B4" value="1009"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="188"/>
                    <measurement group_id="B2" value="182"/>
                    <measurement group_id="B3" value="180"/>
                    <measurement group_id="B4" value="550"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="148"/>
                    <measurement group_id="B2" value="153"/>
                    <measurement group_id="B3" value="158"/>
                    <measurement group_id="B4" value="459"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</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="336"/>
                    <count group_id="B2" value="335"/>
                    <count group_id="B3" value="338"/>
                    <count group_id="B4" value="1009"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="322"/>
                    <measurement group_id="B2" value="322"/>
                    <measurement group_id="B3" value="326"/>
                    <measurement group_id="B4" value="970"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline BCVA measured by the ETDRS letter score</title>
          <description>Visual function of the study eye was assessed at a distance of 4 meters using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).</description>
          <units>scores on a scale</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="336"/>
                    <count group_id="B2" value="335"/>
                    <count group_id="B3" value="338"/>
                    <count group_id="B4" value="1009"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.9" spread="14.0"/>
                    <measurement group_id="B2" value="59.9" spread="13.4"/>
                    <measurement group_id="B3" value="60.0" spread="12.4"/>
                    <measurement group_id="B4" value="59.6" spread="13.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline choroidal neovascularization (CNV) size</title>
          <population>Full analysis set, except 1 participant who did not have a valid baseline measure.</population>
          <units>mm²</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="336"/>
                    <count group_id="B2" value="335"/>
                    <count group_id="B3" value="337"/>
                    <count group_id="B4" value="1008"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.3593" spread="5.0394"/>
                    <measurement group_id="B2" value="5.9768" spread="4.8306"/>
                    <measurement group_id="B3" value="6.5459" spread="5.5315"/>
                    <measurement group_id="B4" value="6.2946" spread="5.1433"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline total lesion area</title>
          <population>Full analysis set, except 2 participants who did not have a valid baseline measure.</population>
          <units>mm²</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="336"/>
                    <count group_id="B2" value="335"/>
                    <count group_id="B3" value="336"/>
                    <count group_id="B4" value="1007"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.8647" spread="5.4145"/>
                    <measurement group_id="B2" value="6.3820" spread="5.0664"/>
                    <measurement group_id="B3" value="6.8814" spread="5.6514"/>
                    <measurement group_id="B4" value="6.7097" spread="5.3827"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline central subfield retinal thickness (CST)</title>
          <population>Full analysis set, except 3 participants who did not have a valid baseline measure.</population>
          <units>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="335"/>
                    <count group_id="B2" value="335"/>
                    <count group_id="B3" value="336"/>
                    <count group_id="B4" value="1006"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="367.1" spread="133.6"/>
                    <measurement group_id="B2" value="370.3" spread="123.7"/>
                    <measurement group_id="B3" value="370.7" spread="132.7"/>
                    <measurement group_id="B4" value="369.3" spread="130.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline NEI-VFQ-25 total score</title>
          <description>NEI-VFQ-25 = National Eye Institute Visual Functioning Questionnaire-25&#xD;
NEI VFQ-25 was a 25-item questionnaire that gave a score on a scale from 0 (worst) to 100 (best = no vision problems)</description>
          <population>Full analysis set, with the participants who completed the NEI-VFQ-25 at baseline.</population>
          <units>scores on a scale</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="317"/>
                    <count group_id="B2" value="321"/>
                    <count group_id="B3" value="316"/>
                    <count group_id="B4" value="954"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="77.8082" spread="14.4206"/>
                    <measurement group_id="B2" value="76.3575" spread="15.1213"/>
                    <measurement group_id="B3" value="77.6670" spread="15.3980"/>
                    <measurement group_id="B4" value="77.2733" spread="14.9843"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48</title>
        <description>Visual function of the study eye was assessed at a distance of 4 meters using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).</description>
        <time_frame>At baseline and Week 48</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept 2q8</title>
            <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept HDq12</title>
            <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
          </group>
          <group group_id="O3">
            <title>Aflibercept HDq16</title>
            <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48</title>
          <description>Visual function of the study eye was assessed at a distance of 4 meters using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).</description>
          <population>Full analysis set</population>
          <units>scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="336"/>
                <count group_id="O2" value="335"/>
                <count group_id="O3" value="338"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.03" spread="0.74"/>
                    <measurement group_id="O2" value="6.06" spread="0.77"/>
                    <measurement group_id="O3" value="5.89" spread="0.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>HDq12 - 2q8</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>One-sided test (alpha=0.025) for non-inferiority at a 4-letter margin</non_inferiority_desc>
            <p_value>0.0009</p_value>
            <p_value_desc>Strictly hierarchical testing procedure to adjust for multiplicity. Since this p-value was below the significance level of 0.025, the fixed sequence testing did continue with the next primary endpoint test (HDq16-2q8)</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Difference in LS means</param_type>
            <param_value>-0.97</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.87</ci_lower_limit>
            <ci_upper_limit>0.92</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>HDq16 - 2q8</groups_desc>
            <non_inferiority_type>Non-Inferiority</non_inferiority_type>
            <non_inferiority_desc>One-sided test (alpha=0.025) for non-inferiority at a 4-letter margin</non_inferiority_desc>
            <p_value>0.0011</p_value>
            <p_value_desc>Strictly hierarchical testing procedure to adjust for multiplicity. Since this p-value was below the significance level of 0.025, the fixed sequence testing did continue with the secondary endpoint test (no IRF and no SRF in central subfield at W16)</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Difference in LS means</param_type>
            <param_value>-1.14</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.97</ci_lower_limit>
            <ci_upper_limit>0.69</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60</title>
        <time_frame>At baseline and Week 60</time_frame>
        <posting_date>10/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16</title>
        <time_frame>At Week 16</time_frame>
        <population>Full analysis set*&#xD;
* The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants due to missing assessment at the respective visit. These participants with missing assessments were not included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept 2q8</title>
            <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept HDq12</title>
            <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
          </group>
          <group group_id="O3">
            <title>Aflibercept HDq16</title>
            <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria.</description>
          </group>
          <group group_id="O4">
            <title>All Aflibercept HD</title>
            <description>Included all participants from aflibercept HDq12 and aflibercept HDq16</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16</title>
          <population>Full analysis set*&#xD;
* The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants due to missing assessment at the respective visit. These participants with missing assessments were not included in the analysis.</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="335"/>
                <count group_id="O2" value="333"/>
                <count group_id="O3" value="334"/>
                <count group_id="O4" value="667"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.6"/>
                    <measurement group_id="O2" value="61.6"/>
                    <measurement group_id="O3" value="65.0"/>
                    <measurement group_id="O4" value="63.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>All HD - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.0002</p_value>
            <p_value_desc>Strictly hierarchical testing procedure to adjust for multiplicity.</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Difference</param_type>
            <param_value>11.733</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>5.263</ci_lower_limit>
            <ci_upper_limit>18.204</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48</title>
        <time_frame>At baseline and Week 48</time_frame>
        <population>Full analysis set*&#xD;
* The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants due to 1 participant per each treatment group with no post-baseline BCVA. These participants with missing assessments were not included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept 2q8</title>
            <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept HDq12</title>
            <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
          </group>
          <group group_id="O3">
            <title>Aflibercept HDq16</title>
            <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48</title>
          <population>Full analysis set*&#xD;
* The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants due to 1 participant per each treatment group with no post-baseline BCVA. These participants with missing assessments were not included in the analysis.</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="335"/>
                <count group_id="O2" value="334"/>
                <count group_id="O3" value="337"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.1"/>
                    <measurement group_id="O2" value="20.7"/>
                    <measurement group_id="O3" value="21.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>HDq12 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.5704</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Difference</param_type>
            <param_value>-1.748</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.784</ci_lower_limit>
            <ci_upper_limit>4.287</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>HDq16 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.7611</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Difference</param_type>
            <param_value>-0.939</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.997</ci_lower_limit>
            <ci_upper_limit>5.119</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48</title>
        <time_frame>At Week 48</time_frame>
        <population>Full analysis set*&#xD;
* The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants due to 1 participant per each treatment group with no post-baseline BCVA. These participants with missing assessments were not included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept 2q8</title>
            <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept HDq12</title>
            <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
          </group>
          <group group_id="O3">
            <title>Aflibercept HDq16</title>
            <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48</title>
          <population>Full analysis set*&#xD;
* The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants due to 1 participant per each treatment group with no post-baseline BCVA. These participants with missing assessments were not included in the analysis.</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="335"/>
                <count group_id="O2" value="334"/>
                <count group_id="O3" value="337"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.9"/>
                    <measurement group_id="O2" value="56.9"/>
                    <measurement group_id="O3" value="54.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>HDq12 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.9554</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Difference</param_type>
            <param_value>-0.182</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.565</ci_lower_limit>
            <ci_upper_limit>6.200</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>HDq16 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.4834</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Difference</param_type>
            <param_value>-2.221</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.435</ci_lower_limit>
            <ci_upper_limit>3.994</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48</title>
        <time_frame>At baseline and Week 48</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept 2q8</title>
            <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept HDq12</title>
            <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
          </group>
          <group group_id="O3">
            <title>Aflibercept HDq16</title>
            <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48</title>
          <population>Full analysis set</population>
          <units>mm^2</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="336"/>
                <count group_id="O2" value="335"/>
                <count group_id="O3" value="338"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.43" spread="0.31"/>
                    <measurement group_id="O2" value="-3.65" spread="0.28"/>
                    <measurement group_id="O3" value="-2.91" spread="0.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>HDq12 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.0009</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Difference in LS means</param_type>
            <param_value>-1.22</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.94</ci_lower_limit>
            <ci_upper_limit>-0.51</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>HDq16 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.2076</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Difference in LS means</param_type>
            <param_value>-0.48</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.22</ci_lower_limit>
            <ci_upper_limit>0.27</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Total Lesion Area From Baseline to Week 48</title>
        <time_frame>At baseline and Week 48</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept 2q8</title>
            <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept HDq12</title>
            <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
          </group>
          <group group_id="O3">
            <title>Aflibercept HDq16</title>
            <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total Lesion Area From Baseline to Week 48</title>
          <population>Full analysis set</population>
          <units>mm^2</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="336"/>
                <count group_id="O2" value="335"/>
                <count group_id="O3" value="338"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.09" spread="0.22"/>
                    <measurement group_id="O2" value="-0.46" spread="0.19"/>
                    <measurement group_id="O3" value="-0.35" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>HDq12 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.0287</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Difference in LS means</param_type>
            <param_value>-0.55</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.04</ci_lower_limit>
            <ci_upper_limit>-0.06</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>HDq16 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.0870</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Difference in LS means</param_type>
            <param_value>-0.44</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.94</ci_lower_limit>
            <ci_upper_limit>0.06</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48</title>
        <time_frame>At Week 48</time_frame>
        <population>Full analysis set*&#xD;
* The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants due to missing assessments at the respective visit. These participants with missing assessments were not included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept 2q8</title>
            <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept HDq12</title>
            <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
          </group>
          <group group_id="O3">
            <title>Aflibercept HDq16</title>
            <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48</title>
          <population>Full analysis set*&#xD;
* The Overall Number of Participants Analyzed is not consistent with numbers provided in the Overall Number of Baseline Participants due to missing assessments at the respective visit. These participants with missing assessments were not included in the analysis.</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="335"/>
                <count group_id="O2" value="332"/>
                <count group_id="O3" value="334"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.4"/>
                    <measurement group_id="O2" value="71.1"/>
                    <measurement group_id="O3" value="66.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>HDq12 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.0015</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Difference</param_type>
            <param_value>11.725</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>4.527</ci_lower_limit>
            <ci_upper_limit>18.923</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>HDq16 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.0458</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Difference</param_type>
            <param_value>7.451</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.142</ci_lower_limit>
            <ci_upper_limit>14.760</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48</title>
        <time_frame>At baseline and Week 48</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept 2q8</title>
            <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept HDq12</title>
            <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
          </group>
          <group group_id="O3">
            <title>Aflibercept HDq16</title>
            <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48</title>
          <population>Full analysis set</population>
          <units>µm</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="336"/>
                <count group_id="O2" value="335"/>
                <count group_id="O3" value="338"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-136.25" spread="4.24"/>
                    <measurement group_id="O2" value="-147.37" spread="4.01"/>
                    <measurement group_id="O3" value="-146.76" spread="3.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>HDq12 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.0283</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Difference in LS means</param_type>
            <param_value>-11.12</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-21.06</ci_lower_limit>
            <ci_upper_limit>-1.18</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>HDq16 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.0321</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Difference in LS means</param_type>
            <param_value>-10.51</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-20.12</ci_lower_limit>
            <ci_upper_limit>-0.90</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48</title>
        <description>NEI VFQ-25 was a 25-item questionnaire that gave a score on a scale from 0 (worst) to 100 (best = no vision problems)</description>
        <time_frame>At baseline and Week 48</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept 2q8</title>
            <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept HDq12</title>
            <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
          </group>
          <group group_id="O3">
            <title>Aflibercept HDq16</title>
            <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48</title>
          <description>NEI VFQ-25 was a 25-item questionnaire that gave a score on a scale from 0 (worst) to 100 (best = no vision problems)</description>
          <population>Full analysis set</population>
          <units>scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="336"/>
                <count group_id="O2" value="335"/>
                <count group_id="O3" value="338"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.22" spread="0.70"/>
                    <measurement group_id="O2" value="3.50" spread="0.70"/>
                    <measurement group_id="O3" value="3.35" spread="0.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>HDq12 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.3817</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Difference in LS means</param_type>
            <param_value>-0.72</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.35</ci_lower_limit>
            <ci_upper_limit>0.90</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>HDq16 - 2q8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>One sided test (alpha = 0.025) for superiority</non_inferiority_desc>
            <p_value>0.3070</p_value>
            <p_value_desc>Nominal p-value, not adjusted for multiplicity</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Difference in LS means</param_type>
            <param_value>-0.87</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.55</ci_lower_limit>
            <ci_upper_limit>0.80</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)</title>
        <time_frame>Up to 156 weeks</time_frame>
        <posting_date>08/2025</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48</title>
        <time_frame>Up to Week 48</time_frame>
        <population>Pharmacokinetic analysis set: included all participants who received any study treatment and who had at least 1 non-missing drug concentration measurement following the first dose of study treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Aflibercept 2q8</title>
            <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4 week intervals</description>
          </group>
          <group group_id="O2">
            <title>Aflibercept HDq12</title>
            <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
          </group>
          <group group_id="O3">
            <title>Aflibercept HDq16</title>
            <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria</description>
          </group>
        </group_list>
        <measure>
          <title>Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48</title>
          <population>Pharmacokinetic analysis set: included all participants who received any study treatment and who had at least 1 non-missing drug concentration measurement following the first dose of study treatment</population>
          <units>mg/L</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="308"/>
                <count group_id="O2" value="313"/>
                <count group_id="O3" value="313"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="287"/>
                    <count group_id="O2" value="295"/>
                    <count group_id="O3" value="299"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not calculated (less than 2/3 of values per timepoint are &gt;= Lower level of quantification (LLOQ) for geometric mean calculation).</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Not calculated (less than 2/3 of values per timepoint are &gt;= Lower level of quantification (LLOQ) for geometric mean calculation).</measurement>
                    <measurement group_id="O3" value="NA" spread="NA">Not calculated (less than 2/3 of values per timepoint are &gt;= Lower level of quantification (LLOQ) for geometric mean calculation).</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5: within 3 to 7 days after the Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="259"/>
                    <count group_id="O2" value="267"/>
                    <count group_id="O3" value="259"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.03" spread="69.64"/>
                    <measurement group_id="O2" value="0.14" spread="78.92"/>
                    <measurement group_id="O3" value="0.12" spread="82.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="285"/>
                    <count group_id="O2" value="288"/>
                    <count group_id="O3" value="299"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not calculated (less than 2/3 of values per timepoint are &gt;= Lower level of quantification (LLOQ) for geometric mean calculation).</measurement>
                    <measurement group_id="O2" value="0.02" spread="81.73"/>
                    <measurement group_id="O3" value="0.02" spread="84.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="258"/>
                    <count group_id="O2" value="284"/>
                    <count group_id="O3" value="276"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not calculated (less than 2/3 of values per timepoint are &gt;= Lower level of quantification (LLOQ) for geometric mean calculation).</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Not calculated (less than 2/3 of values per timepoint are &gt;= Lower level of quantification (LLOQ) for geometric mean calculation).</measurement>
                    <measurement group_id="O3" value="NA" spread="NA">Not calculated (less than 2/3 of values per timepoint are &gt;= Lower level of quantification (LLOQ) for geometric mean calculation).</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="253"/>
                    <count group_id="O2" value="265"/>
                    <count group_id="O3" value="261"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">Not calculated (less than 2/3 of values per timepoint are &gt;= Lower level of quantification (LLOQ) for geometric mean calculation).</measurement>
                    <measurement group_id="O2" value="NA" spread="NA">Not calculated (less than 2/3 of values per timepoint are &gt;= Lower level of quantification (LLOQ) for geometric mean calculation).</measurement>
                    <measurement group_id="O3" value="NA" spread="NA">Not calculated (less than 2/3 of values per timepoint are &gt;= Lower level of quantification (LLOQ) for geometric mean calculation).</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through End of Masked Study</title>
        <time_frame>Up to week 96</time_frame>
        <posting_date>08/2025</posting_date>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dosing up to 30 days after last dosing (active injection or sham procedure), up to Week 48. AE reporting for all-cause mortality considers all deaths occurred at any time during the study before the last contact, up to Week 48.</time_frame>
      <desc>Incidences of ocular TEAEs include both study and fellow eye TEAEs.</desc>
      <group_list>
        <group group_id="E1">
          <title>Aflibercept 2q8</title>
          <description>Participants received aflibercept 2 mg administered every 8 weeks after 3 initial injections at 4-week intervals</description>
        </group>
        <group group_id="E2">
          <title>Aflibercept HDq12</title>
          <description>Participants received high dose (HD) aflibercept administered every 12 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified dose regimen modification (DRM) criteria</description>
        </group>
        <group group_id="E3">
          <title>Aflibercept HDq16</title>
          <description>Participants received high dose (HD) aflibercept administered every 16 weeks after 3 initial injections at 4-week intervals. Participants in this group can have their treatment intervals adjusted according to pre-specified DRM criteria</description>
        </group>
        <group group_id="E4">
          <title>All Aflibercept HD</title>
          <description>Included all participants from aflibercept HDq12 and aflibercept HDq16</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (25.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="336"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="335"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="49" subjects_at_risk="336"/>
                <counts group_id="E2" subjects_affected="41" subjects_at_risk="335"/>
                <counts group_id="E3" subjects_affected="37" subjects_at_risk="338"/>
                <counts group_id="E4" subjects_affected="78" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood loss anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="338"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Cardiac failure chronic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Myocardial ischaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Acute left ventricular failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Angle closure glaucoma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Choroidal detachment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Retinal detachment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Retinal haemorrhage</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Retinal vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Vitreous haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Colitis ischaemic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Enteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Oesophagitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Umbilical hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Mechanical ileus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Large intestine polyp</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Abdominal strangulated hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct stone</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Erysipelas</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="338"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Q fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Systemic infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="673"/>
              </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" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Ligament sprain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Patella fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Spinal compression fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Thoracic vertebral fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Pelvic fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Skull fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Upper limb fracture</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Intraocular pressure increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="338"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Malnutrition</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="3" subjects_affected="2" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Exostosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Lumbar spinal stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Osteitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="338"/>
                <counts group_id="E4" events="4" subjects_affected="3" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Rotator cuff syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Spinal osteoarthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Mobility decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Vertebral foraminal stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Bladder cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Bladder neoplasm</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Bone neoplasm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Breast cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Colon cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Endometrial adenocarcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Endometrial cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Gastric cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Hypopharyngeal cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Lung carcinoma cell type unspecified stage IV</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Non-Hodgkin's lymphoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Rectal adenocarcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Penile squamous cell carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Malignant peritoneal neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Metastatic neoplasm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Neoplasm progression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Non-small cell lung cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Head and neck cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Adenocarcinoma metastatic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Loss of consciousness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Vertebrobasilar insufficiency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Lumbar radiculopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Stroke in evolution</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Cystitis haemorrhagic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Renal cyst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Prostatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Pleurisy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Nasal cyst</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Inguinal hernia repair</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Artificial urinary sphincter implant</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="336"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Pain management</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Venous thrombosis limb</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="336"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="335"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="338"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (25.0)</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="62" subjects_at_risk="336"/>
                <counts group_id="E2" subjects_affected="58" subjects_at_risk="335"/>
                <counts group_id="E3" subjects_affected="78" subjects_at_risk="338"/>
                <counts group_id="E4" subjects_affected="136" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Retinal haemorrhage</sub_title>
                <counts group_id="E1" events="19" subjects_affected="17" subjects_at_risk="336"/>
                <counts group_id="E2" events="22" subjects_affected="21" subjects_at_risk="335"/>
                <counts group_id="E3" events="10" subjects_affected="9" subjects_at_risk="338"/>
                <counts group_id="E4" events="32" subjects_affected="30" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Visual acuity reduced</sub_title>
                <counts group_id="E1" events="32" subjects_affected="26" subjects_at_risk="336"/>
                <counts group_id="E2" events="19" subjects_affected="16" subjects_at_risk="335"/>
                <counts group_id="E3" events="27" subjects_affected="21" subjects_at_risk="338"/>
                <counts group_id="E4" events="46" subjects_affected="37" subjects_at_risk="673"/>
              </event>
              <event>
                <sub_title>Neovascular age-related macular degeneration</sub_title>
                <counts group_id="E1" events="17" subjects_affected="16" subjects_at_risk="336"/>
                <counts group_id="E2" events="22" subjects_affected="19" subjects_at_risk="335"/>
                <counts group_id="E3" events="32" subjects_affected="32" subjects_at_risk="338"/>
                <counts group_id="E4" events="54" subjects_affected="51" subjects_at_risk="673"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="336"/>
                <counts group_id="E2" events="10" subjects_affected="10" subjects_at_risk="335"/>
                <counts group_id="E3" events="21" subjects_affected="20" subjects_at_risk="338"/>
                <counts group_id="E4" events="31" subjects_affected="30" subjects_at_risk="673"/>
              </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>The only disclosure restriction on the PI is that 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. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Therapeutic Area Head</name_or_title>
      <organization>Bayer</organization>
      <phone>(+) 1-888-8422937</phone>
      <email>clinical-trials-contact@bayer.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/NCT04423718
org study id: 20968
secondary id: 2019-003851-12
nct id: NCT04423718
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
In this study researchers want to learn more about changes in visual acuity (clarity of
      vision) with a high dose treatment with Aflibercept (Eylea) in patients suffering from
      neovascular age-related macular degeneration (nAMD). Neovascular AMD is an eye disease that
      causes blurred vision or a blind spot due to abnormal blood vessels that leak fluid or blood
      into the light sensitive lining inside the eye (retina). The fluid buildup causes the central
      part of the retina (macula) responsible for sharp, straight-ahead vision to swell and thicken
      (edema), which distorts vision.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Up to Week 108: Participant and Investigator masked. Week 108 to Week 156: Participant and Investigator unmasked to treatment intervals.
measure: Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48
time frame: At baseline and Week 48
description: Visual function of the study eye was assessed at a distance of 4 meters using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best).
measure: Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60
time frame: At baseline and Week 60
measure: Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16
time frame: At Week 16
measure: Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48
time frame: At baseline and Week 48
measure: Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48
time frame: At Week 48
measure: Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48
time frame: At baseline and Week 48
measure: Change in Total Lesion Area From Baseline to Week 48
time frame: At baseline and Week 48
measure: Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48
time frame: At Week 48
measure: Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48
time frame: At baseline and Week 48
measure: Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48
time frame: At baseline and Week 48
description: NEI VFQ-25 was a 25-item questionnaire that gave a score on a scale from 0 (worst) to 100 (best = no vision problems)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)
time frame: Up to 156 weeks
measure: Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48
time frame: Up to Week 48
measure: Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through End of Masked Study
time frame: Up to week 96
arm group label: Aflibercept 2q8
arm group type: Active Comparator
description: In the double-masked study part (Years 1 and 2), Aflibercept 2 mg administered every 8 weeks after a loading phase. (Active Comparator) In Year 3, high dose aflibercept administered according to individual patient response. (Experimental)
arm group label: Aflibercept HDq12
arm group type: Experimental
description: Aflibercept high dose (HD) administered every 12 weeks after an initiation phase. Treatment intervals adjusted according to individual patient response.
arm group label: Aflibercept HDq16
arm group type: Experimental
description: Aflibercept high dose administered every 16 weeks after an initiation phase. Treatment intervals adjusted according to individual patient response.
intervention type: Drug
intervention name: Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)
description: Solution in Vial, intravitreal (IVT) injection
arm group label: Aflibercept 2q8
arm group label: Aflibercept HDq12
arm group label: Aflibercept HDq16
intervention type: Drug
intervention name: Aflibercept VEGF Trap-Eye (Eylea, BAY86-5321)
description: Solution in Vial, 2 mg, intravitreal (IVT) injection
arm group label: Aflibercept 2q8
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
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country: Argentina
country: Australia
country: Austria
country: Bulgaria
country: Canada
country: China
country: Czechia
country: Estonia
country: France
country: Georgia
country: Hungary
country: Israel
country: Italy
country: Japan
country: Korea, Republic of
country: Latvia
country: Lithuania
country: Portugal
country: Russian Federation
country: Serbia
country: Singapore
country: Slovakia
country: Spain
country: Switzerland
country: Taiwan
country: Ukraine
country: United States
country: Belgium
country: Colombia
country: Denmark
country: Germany
country: Hong Kong
country: Netherlands
country: Turkey
country: United Kingdom
url: https://clinicaltrials.bayer.com/
description: Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: Wet Macular Degeneration
mesh term: Aflibercept
sharing ipd: No
ipd description: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.
Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 