<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/NCT02222207</url>
  </required_header>
  <id_info>
    <org_study_id>15984</org_study_id>
    <secondary_id>2012-003763-22</secondary_id>
    <nct_id>NCT02222207</nct_id>
  </id_info>
  <brief_title>Regorafenib Eye Drops: Investigation of Efficacy and Safety in Neovascular Age Related Macular Degeneration</brief_title>
  <acronym>DREAM</acronym>
  <official_title>A Combined Phase IIa / IIb Study of the Efficacy, Safety, and Tolerability of Repeated Topical Doses of Regorafenib Eye Drops, in Treatment-naïve Subjects With Neovascular Age Related Macular Degeneration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bayer</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Part A (Phase IIa):&#xD;
&#xD;
      Primary objectives:&#xD;
&#xD;
      The study part A is designed to investigate whether the use of regorafenib eye drops can help&#xD;
      patients with neovascular (wet) Age-Related Macular Degeneration (wAMD) to see better after 4&#xD;
      weeks and 12 weeks after inclusion into this study.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
      The study will also evaluate the safety and tolerability of the regorafenib eye drops.&#xD;
&#xD;
      Part B (Phase IIb):&#xD;
&#xD;
      Primary objectives:&#xD;
&#xD;
      The study part B is designed to investigate:&#xD;
&#xD;
        -  how often the regorafenib eye drops need to be given per day&#xD;
&#xD;
        -  whether the use of regorafenib eye drops can help patients with neovascular (wet)&#xD;
           Age-Related Macular Degeneration (wAMD) to see better after 4 weeks and 12 weeks after&#xD;
           inclusion into this study.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
      The study will also evaluate how the different dosings of regorafenib eye drops affect&#xD;
      patients vision, the safety and the tolerability.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <phase>Phase 2</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>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Study Week 4 for Study Part A</measure>
    <time_frame>Baseline, Week 4</time_frame>
    <description>Participants will be assessed at each clinic visit for best corrected visual acuity using the early treatment diabetic retinopathy study chart. Visual function of the study eye and the fellow eye was assessed using the ETDRS. The participant's ETDRS testing score was recorded in the appropriate eCRF page at each study visit. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward. A higher score represents better functioning.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in BCVA as Measured by ETDRS Letter Score at Study Week 12 for Study Part A</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Participants were assessed at each clinic visit for best corrected visual acuity using the early treatment diabetic retinopathy study chart. Visual function of the study eye and the fellow eye was assessed using the ETDRS protocol. ETDRS testing score was recorded in the appropriate eCRF page at each study visit. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward. A higher score represents better functioning.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Individual Changes in BCVA of Greater Than Equal to (&gt;=) 0 Letters of Vision From Study Week 4 to Week 12 for Study Part A</measure>
    <time_frame>Week 4, Week 12</time_frame>
    <description>Participants were assessed at each clinic visit for BCVA using the early treatment diabetic retinopathy study chart. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With a Loss in BCVA of &gt;= 10 Letters From Baseline to Study Week 12 for Study Part A</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Participants were assessed at each clinic visit for BCVA using the early treatment diabetic retinopathy study chart. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>Macular Degeneration</condition>
  <arm_group>
    <arm_group_label>Regorafenib [A]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part A: Patients will receive Regorafenib eye drops</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regorafenib [B1]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part B: Regorafenib eye drops dose 1; plus sham IVT (Intravitreal therapy) once every 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regorafenib [B2]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part B: Regorafenib eye drops dose 2; plus sham IVT (Intravitreal therapy) once every 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regorafenib [B3]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part B: Regorafenib eye drops dose 3; plus sham IVT (Intravitreal therapy) once every 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regorafenib [B4]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part B: Regorafenib eye drops dose 4; plus sham IVT (Intravitreal therapy) once every 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regorafenib [B5]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part B: Regorafenib eye drops dose 5; plus sham IVT (Intravitreal therapy) once every 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Regorafenib [B6]</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part B: Regorafenib eye drops dose 6; plus sham IVT (Intravitreal therapy) once every 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ranibizumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ranibizumab IVT once every 4 weeks; plus placebo eye drops to match the regorafenib eye drop regimens</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Regorafenib, ophthalmic oily suspension (BAY73-4506)</intervention_name>
    <description>Subjects receive Regorafenib as eye drops</description>
    <arm_group_label>Regorafenib [A]</arm_group_label>
    <arm_group_label>Regorafenib [B1]</arm_group_label>
    <arm_group_label>Regorafenib [B2]</arm_group_label>
    <arm_group_label>Regorafenib [B3]</arm_group_label>
    <arm_group_label>Regorafenib [B4]</arm_group_label>
    <arm_group_label>Regorafenib [B5]</arm_group_label>
    <arm_group_label>Regorafenib [B6]</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sham IVT</intervention_name>
    <description>Sham injections</description>
    <arm_group_label>Regorafenib [B1]</arm_group_label>
    <arm_group_label>Regorafenib [B2]</arm_group_label>
    <arm_group_label>Regorafenib [B3]</arm_group_label>
    <arm_group_label>Regorafenib [B4]</arm_group_label>
    <arm_group_label>Regorafenib [B5]</arm_group_label>
    <arm_group_label>Regorafenib [B6]</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ranibizumab</intervention_name>
    <description>Subjects receive Ranibizumab as intravitreal injection</description>
    <arm_group_label>Ranibizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo eye drops</description>
    <arm_group_label>Ranibizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to read (or, if unable to read due to visual impairment, be read to verbatim by&#xD;
             the person administering the informed consent or a family member) and able to&#xD;
             understand the informed consent form (ICF)&#xD;
&#xD;
          -  Men and women ≥ 50 years of age&#xD;
&#xD;
          -  Active primary subfoveal CNV (Choroidal neovascularization) lesions secondary to AMD&#xD;
             (Age-related macular degeneration), including juxtafoveal lesions that affect the&#xD;
             fovea as evidenced by FA (Fluorescein angiography) in the study eye and reviewed by&#xD;
             the central reading center&#xD;
&#xD;
          -  The area of CNV must occupy at least 50% of total lesion in the study eye, as&#xD;
             determined by FA review at the central reading center&#xD;
&#xD;
          -  Evidence of intraretinal and/or subretinal fluid on OCT (Optical coherence tomography)&#xD;
&#xD;
          -  Early Treatment Diabetic Retinopathy Study BCVA of 73 to 25 letters (20/40 to 20/320&#xD;
             Snellen equivalent) in the study eye&#xD;
&#xD;
          -  Willing, committed, and able to return for all clinic visits and complete all study&#xD;
             related procedures&#xD;
&#xD;
          -  Women of childbearing potential and men must agree to use adequate contraception when&#xD;
             sexually active. This applies since signing of the ICF until one month after the EOS&#xD;
             (end of study) visit. The definition of adequate contraception will be based on the&#xD;
             judgment of the investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concurrent disease in the study eye, other than AMD (e.g., corneal diseases and&#xD;
             dystrophies, conjunctival diseases, eye lid abnormalities, or any other diseases of&#xD;
             the cornea and macula, or optic nerve abnormality) that could compromise visual&#xD;
             acuity, likely require medical or surgical intervention during the study period, would&#xD;
             limit the potential to gain or lose vision during study treatment, or could otherwise&#xD;
             confound interpretation of the results&#xD;
&#xD;
          -  Total lesion size (including neovascularization, scar, blood) &gt; 12 disc areas (30.5&#xD;
             mm2) as assessed by FA&#xD;
&#xD;
          -  Only one functional eye, even if that eye is otherwise eligible for the study&#xD;
&#xD;
          -  Prior ocular or systemic treatment or surgery for neovascular AMD in the study eye&#xD;
             except dietary supplements or vitamins&#xD;
&#xD;
          -  Prior treatment with any systemic anti-VEGF (Vascular endothelial growth factor) agent&#xD;
&#xD;
          -  Use of systemic or ocular treatment with an investigational drug within 12 weeks prior&#xD;
             to start of study treatment&#xD;
&#xD;
          -  Any other condition that would require frequent chronic co-administration of other&#xD;
             topical eye medications that would interfere with study drug administration (e.g.&#xD;
             contact lens)&#xD;
&#xD;
          -  Symptoms or conditions consistent with contraindications listed in the current local&#xD;
             label for ranibizumab&#xD;
&#xD;
          -  Participation in an investigational study within 30 days prior to start of study&#xD;
             treatment that involved treatment with any drug (excluding vitamins and minerals) or&#xD;
             device&#xD;
&#xD;
          -  Lactating women and women of child-bearing potential with either a positive pregnancy&#xD;
             test result or no pregnancy test at screening are excluded. Postmenopausal women must&#xD;
             be amenorrheic for at least 12 months in order not to be considered of child bearing&#xD;
             potential.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bayer Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Bayer</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Arcadia</city>
        <state>California</state>
        <zip>91007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Campbell</city>
        <state>California</state>
        <zip>95008</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Costa Mesa</city>
        <state>California</state>
        <zip>92626</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Laguna Hills</city>
        <state>California</state>
        <zip>92653</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Mountain View</city>
        <state>California</state>
        <zip>94040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Santa Ana</city>
        <state>California</state>
        <zip>92705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Golden</city>
        <state>Colorado</state>
        <zip>80401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boynton Beach</city>
        <state>Florida</state>
        <zip>33426</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Plantation</city>
        <state>Florida</state>
        <zip>33324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Stuart</city>
        <state>Florida</state>
        <zip>34994</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Winter Haven</city>
        <state>Florida</state>
        <zip>33880</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New Albany</city>
        <state>Indiana</state>
        <zip>47150</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Leawood</city>
        <state>Kansas</state>
        <zip>66211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Eunice</city>
        <state>Louisiana</state>
        <zip>70535</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49525</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Florissant</city>
        <state>Missouri</state>
        <zip>63031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Teaneck</city>
        <state>New Jersey</state>
        <zip>07666</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <zip>28803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>West Mifflin</city>
        <state>Pennsylvania</state>
        <zip>15122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rapid City</city>
        <state>South Dakota</state>
        <zip>57701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>McAllen</city>
        <state>Texas</state>
        <zip>78503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <zip>76508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77384</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Strathfield</city>
        <state>New South Wales</state>
        <zip>2135</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Parramatta</city>
        <zip>2150</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wien</city>
        <zip>1130</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2H 0C8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T5H 0X5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 3N9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 2Y9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
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  </location>
  <location>
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      <address>
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  <location>
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      <address>
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  </location>
  <location>
    <facility>
      <address>
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  <location>
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      <address>
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  <location>
    <facility>
      <address>
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  <location>
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      <address>
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  <location>
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  <location>
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    <facility>
      <address>
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  <location>
    <facility>
      <address>
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  <location>
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      <address>
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  <location>
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  <location>
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      <address>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
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  <location>
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  <location>
    <facility>
      <address>
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  <location>
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      <address>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
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  <location>
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      <address>
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      <address>
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    <facility>
      <address>
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  <location>
    <facility>
      <address>
        <city>Budapest</city>
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  <location>
    <facility>
      <address>
        <city>Budapest</city>
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  <location>
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      <address>
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  <location>
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      <address>
        <city>Pecs</city>
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      <address>
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  <location>
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      <address>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
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  <location>
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      <address>
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      <address>
        <city>Kfar Saba</city>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
        <city>Rehovot</city>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
        <city>Zerifin</city>
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  <location>
    <facility>
      <address>
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    </facility>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
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  <location>
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      <address>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
      <address>
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        <state>Toscana</state>
        <zip>50134</zip>
        <country>Italy</country>
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  <location>
    <facility>
      <address>
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        <state>Veneto</state>
        <zip>35128</zip>
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  <location>
    <facility>
      <address>
        <city>Ancona</city>
        <zip>60126</zip>
        <country>Italy</country>
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  <location>
    <facility>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
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  <location>
    <facility>
      <address>
        <city>Milano</city>
        <zip>20132</zip>
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  <location>
    <facility>
      <address>
        <city>Sassari</city>
        <zip>07100</zip>
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  <location>
    <facility>
      <address>
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        <state>Chiba</state>
        <zip>285-0922</zip>
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  <location>
    <facility>
      <address>
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        <state>Fukuoka</state>
        <zip>800-0344</zip>
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  <location>
    <facility>
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  <location>
    <facility>
      <address>
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  <location>
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      <address>
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        <state>Hyogo</state>
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  <location>
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        <zip>242-0001</zip>
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  <location>
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      <address>
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        <country>Japan</country>
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  <location>
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        <state>Mie</state>
        <zip>518-0842</zip>
        <country>Japan</country>
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  <location>
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      <address>
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        <state>Tokyo</state>
        <zip>182-0024</zip>
        <country>Japan</country>
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  </location>
  <location>
    <facility>
      <address>
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        <state>Tokyo</state>
        <zip>173-0015</zip>
        <country>Japan</country>
      </address>
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  <location>
    <facility>
      <address>
        <city>Ota-ku</city>
        <state>Tokyo</state>
        <zip>143-0013</zip>
        <country>Japan</country>
      </address>
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  <location>
    <facility>
      <address>
        <city>Taito-ku</city>
        <state>Tokyo</state>
        <zip>111-0051</zip>
        <country>Japan</country>
      </address>
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  <location>
    <facility>
      <address>
        <city>Fukuoka</city>
        <zip>812-0011</zip>
        <country>Japan</country>
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  <location>
    <facility>
      <address>
        <city>Kumamoto</city>
        <zip>860-0027</zip>
        <country>Japan</country>
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  <location>
    <facility>
      <address>
        <city>Nagasaki</city>
        <zip>852-8511</zip>
        <country>Japan</country>
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  <location>
    <facility>
      <address>
        <city>Nara</city>
        <zip>630-8305</zip>
        <country>Japan</country>
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  <location>
    <facility>
      <address>
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        <zip>530-0001</zip>
        <country>Japan</country>
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  <location>
    <facility>
      <address>
        <city>Osaka</city>
        <zip>533-0024</zip>
        <country>Japan</country>
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      <address>
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        <state>Gyeonggido</state>
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      <address>
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        <zip>49241</zip>
        <country>Korea, Republic of</country>
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  <location>
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      <address>
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        <zip>405-760</zip>
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      <address>
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        <zip>03080</zip>
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  <location>
    <facility>
      <address>
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  <location>
    <facility>
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  <location>
    <facility>
      <address>
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        <zip>137-701</zip>
        <country>Korea, Republic of</country>
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        <zip>85107</zip>
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  <location>
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        <zip>03426</zip>
        <country>Slovakia</country>
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  <location>
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      <address>
        <city>Trencin</city>
        <zip>91171</zip>
        <country>Slovakia</country>
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        <zip>01008</zip>
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  <location>
    <facility>
      <address>
        <city>Zilina</city>
        <zip>01207</zip>
        <country>Slovakia</country>
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  <location>
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        <state>Barcelona</state>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
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  <location>
    <facility>
      <address>
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        <state>Barcelona</state>
        <zip>08190</zip>
        <country>Spain</country>
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  <location>
    <facility>
      <address>
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        <state>Vizcaya</state>
        <zip>48903</zip>
        <country>Spain</country>
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  <location>
    <facility>
      <address>
        <city>Albacete</city>
        <zip>02006</zip>
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  <location>
    <facility>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
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      <address>
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        <zip>41013</zip>
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    <facility>
      <address>
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        <zip>41071</zip>
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        <zip>46014</zip>
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  <location>
    <facility>
      <address>
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        <zip>46015</zip>
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      <address>
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        <zip>47012</zip>
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    <facility>
      <address>
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        <zip>3010</zip>
        <country>Switzerland</country>
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  </location>
  <location>
    <facility>
      <address>
        <city>Lausanne</city>
        <zip>1004</zip>
        <country>Switzerland</country>
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  </location>
  <location>
    <facility>
      <address>
        <city>Zürich</city>
        <zip>8063</zip>
        <country>Switzerland</country>
      </address>
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  </location>
  <location_countries>
    <country>Australia</country>
    <country>Austria</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>Colombia</country>
    <country>Czech Republic</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hong Kong</country>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Slovakia</country>
    <country>Spain</country>
    <country>Switzerland</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2016</verification_date>
  <study_first_submitted>August 20, 2014</study_first_submitted>
  <study_first_submitted_qc>August 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <results_first_submitted>June 11, 2016</results_first_submitted>
  <results_first_submitted_qc>July 25, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">September 8, 2016</results_first_posted>
  <disposition_first_submitted>October 12, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>October 12, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">November 4, 2015</disposition_first_posted>
  <last_update_submitted>July 25, 2016</last_update_submitted>
  <last_update_submitted_qc>July 25, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 8, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>neovascular Age-related Macular Degeneration</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>Ranibizumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 27 centers, between 10 October 2014 (first subject first visit) and 17 June 2015 (last subject last visit).</recruitment_details>
      <pre_assignment_details>Study was planned to be conducted in 2 parts, Part A and B, in Part A 89 subjects were enrolled, of them 37 were screen failure and 52 were assigned to treatment, 1 subject was excluded from all analysis sets due to protocol deviations and 51 subjects were analyzed. Part B was not initiated and the study terminated following completion of Part A.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part A Regorafenib</title>
          <description>Participants self-administered 30 milligram per milliliter (mg/mL), 25 microliter (mcL),1 drop of Regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated and Valid for Full Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="48"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other reasons</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Part A Regorafenib</title>
          <description>Participants self-administered 30 milligram per milliliter (mg/mL), 25 microliter (mcL),1 drop of Regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="51"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75" 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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Study Week 4 for Study Part A</title>
        <description>Participants will be assessed at each clinic visit for best corrected visual acuity using the early treatment diabetic retinopathy study chart. Visual function of the study eye and the fellow eye was assessed using the ETDRS. The participant's ETDRS testing score was recorded in the appropriate eCRF page at each study visit. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward. A higher score represents better functioning.</description>
        <time_frame>Baseline, Week 4</time_frame>
        <population>Full Analysis Set (FAS): included participants who received at least one dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A Regorafenib</title>
            <description>Participants self-administered 30 milligram per milliliter (mg/mL), 25 microliter (mcL),1 drop of Regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Study Week 4 for Study Part A</title>
          <description>Participants will be assessed at each clinic visit for best corrected visual acuity using the early treatment diabetic retinopathy study chart. Visual function of the study eye and the fellow eye was assessed using the ETDRS. The participant's ETDRS testing score was recorded in the appropriate eCRF page at each study visit. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward. A higher score represents better functioning.</description>
          <population>Full Analysis Set (FAS): included participants who received at least one dose of study medication.</population>
          <units>Score on scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.18" spread="7.55" lower_limit="7.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in BCVA as Measured by ETDRS Letter Score at Study Week 12 for Study Part A</title>
        <description>Participants were assessed at each clinic visit for best corrected visual acuity using the early treatment diabetic retinopathy study chart. Visual function of the study eye and the fellow eye was assessed using the ETDRS protocol. ETDRS testing score was recorded in the appropriate eCRF page at each study visit. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward. A higher score represents better functioning.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>Full Analysis Set (FAS): included subjects who received at least one dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A Regorafenib</title>
            <description>Participants self-administered 30 milligram per milliliter (mg/mL), 25 microliter (mcL),1 drop of Regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in BCVA as Measured by ETDRS Letter Score at Study Week 12 for Study Part A</title>
          <description>Participants were assessed at each clinic visit for best corrected visual acuity using the early treatment diabetic retinopathy study chart. Visual function of the study eye and the fellow eye was assessed using the ETDRS protocol. ETDRS testing score was recorded in the appropriate eCRF page at each study visit. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward. A higher score represents better functioning.</description>
          <population>Full Analysis Set (FAS): included subjects who received at least one dose of study medication.</population>
          <units>Score on scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.36" spread="7.68" lower_limit="7.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Individual Changes in BCVA of Greater Than Equal to (&gt;=) 0 Letters of Vision From Study Week 4 to Week 12 for Study Part A</title>
        <description>Participants were assessed at each clinic visit for BCVA using the early treatment diabetic retinopathy study chart. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.</description>
        <time_frame>Week 4, Week 12</time_frame>
        <population>Full Analysis Set (FAS): included subjects who received at least one dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A Regorafenib</title>
            <description>Participants self-administered 30 milligram per milliliter (mg/mL), 25 microliter (mcL),1 drop of Regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Individual Changes in BCVA of Greater Than Equal to (&gt;=) 0 Letters of Vision From Study Week 4 to Week 12 for Study Part A</title>
          <description>Participants were assessed at each clinic visit for BCVA using the early treatment diabetic retinopathy study chart. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.</description>
          <population>Full Analysis Set (FAS): included subjects who received at least one dose of study medication.</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="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With a Loss in BCVA of &gt;= 10 Letters From Baseline to Study Week 12 for Study Part A</title>
        <description>Participants were assessed at each clinic visit for BCVA using the early treatment diabetic retinopathy study chart. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>Full Analysis Set (FAS): included subjects who received at least one dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A Regorafenib</title>
            <description>Participants self-administered 30 milligram per milliliter (mg/mL), 25 microliter (mcL),1 drop of Regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With a Loss in BCVA of &gt;= 10 Letters From Baseline to Study Week 12 for Study Part A</title>
          <description>Participants were assessed at each clinic visit for BCVA using the early treatment diabetic retinopathy study chart. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.</description>
          <population>Full Analysis Set (FAS): included subjects who received at least one dose of study medication.</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="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the start of study treatment until 30 days after last dose of study drug treatment (up to Week 16).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Part A Regorafenib</title>
          <description>Participants self-administered 30 mg/mL, 25 mcL, 1 drop of regorafenib eye drops, topically thrice daily (TID) to the study eye for 12 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (18.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Visual acuity tests abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (18.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Visual acuity reduced</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Visual acuity tests abnormal</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="51"/>
              </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>In mulit centre studies result of study are to be published only through coordination by Bayer in order to combine the results of all centres. Center free to publish its results provided the overall results have not been published within 18 months from study completion (data base lock), subject to the compliance to remaining terms set forth in the PI contract.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>As the study was prematurely terminated since pre-defined proof of concept (PoC) criteria were not met in Part A, hence part B was not initiated. Part B related end points and data were not reported since it is not conducted.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Therapeutic Area Head</name_or_title>
      <organization>BAYER</organization>
      <email>Clinical-Trial-Disclosure@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/NCT02222207
org study id: 15984
secondary id: 2012-003763-22
nct id: NCT02222207
lead sponsor: 
has dmc: Yes
Part A (Phase IIa):

      Primary objectives:

      The study part A is designed to investigate whether the use of regorafenib eye drops can help
      patients with neovascular (wet) Age-Related Macular Degeneration (wAMD) to see better after 4
      weeks and 12 weeks after inclusion into this study.

      Secondary objectives:

      The study will also evaluate the safety and tolerability of the regorafenib eye drops.

      Part B (Phase IIb):

      Primary objectives:

      The study part B is designed to investigate:

        -  how often the regorafenib eye drops need to be given per day

        -  whether the use of regorafenib eye drops can help patients with neovascular (wet)
           Age-Related Macular Degeneration (wAMD) to see better after 4 weeks and 12 weeks after
           inclusion into this study.

      Secondary objectives:

      The study will also evaluate how the different dosings of regorafenib eye drops affect
      patients vision, the safety and the tolerability.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Study Week 4 for Study Part A
time frame: Baseline, Week 4
description: Participants will be assessed at each clinic visit for best corrected visual acuity using the early treatment diabetic retinopathy study chart. Visual function of the study eye and the fellow eye was assessed using the ETDRS. The participant's ETDRS testing score was recorded in the appropriate eCRF page at each study visit. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward. A higher score represents better functioning.
measure: Change From Baseline in BCVA as Measured by ETDRS Letter Score at Study Week 12 for Study Part A
time frame: Baseline, Week 12
description: Participants were assessed at each clinic visit for best corrected visual acuity using the early treatment diabetic retinopathy study chart. Visual function of the study eye and the fellow eye was assessed using the ETDRS protocol. ETDRS testing score was recorded in the appropriate eCRF page at each study visit. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward. A higher score represents better functioning.
measure: Percentage of Participants With Individual Changes in BCVA of Greater Than Equal to (>=) 0 Letters of Vision From Study Week 4 to Week 12 for Study Part A
time frame: Week 4, Week 12
description: Participants were assessed at each clinic visit for BCVA using the early treatment diabetic retinopathy study chart. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.
measure: Percentage of Participants With a Loss in BCVA of >= 10 Letters From Baseline to Study Week 12 for Study Part A
time frame: Baseline, Week 12
description: Participants were assessed at each clinic visit for BCVA using the early treatment diabetic retinopathy study chart. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.
arm group label: Regorafenib [A]
arm group type: Experimental
description: Part A: Patients will receive Regorafenib eye drops
arm group label: Regorafenib [B1]
arm group type: Experimental
description: Part B: Regorafenib eye drops dose 1; plus sham IVT (Intravitreal therapy) once every 4 weeks
arm group label: Regorafenib [B2]
arm group type: Experimental
description: Part B: Regorafenib eye drops dose 2; plus sham IVT (Intravitreal therapy) once every 4 weeks
arm group label: Regorafenib [B3]
arm group type: Experimental
description: Part B: Regorafenib eye drops dose 3; plus sham IVT (Intravitreal therapy) once every 4 weeks
arm group label: Regorafenib [B4]
arm group type: Experimental
description: Part B: Regorafenib eye drops dose 4; plus sham IVT (Intravitreal therapy) once every 4 weeks
arm group label: Regorafenib [B5]
arm group type: Experimental
description: Part B: Regorafenib eye drops dose 5; plus sham IVT (Intravitreal therapy) once every 4 weeks
arm group label: Regorafenib [B6]
arm group type: Experimental
description: Part B: Regorafenib eye drops dose 6; plus sham IVT (Intravitreal therapy) once every 4 weeks
arm group label: Ranibizumab
arm group type: Active Comparator
description: Ranibizumab IVT once every 4 weeks; plus placebo eye drops to match the regorafenib eye drop regimens
intervention type: Drug
intervention name: Regorafenib, ophthalmic oily suspension (BAY73-4506)
description: Subjects receive Regorafenib as eye drops
arm group label: Regorafenib [A]
arm group label: Regorafenib [B1]
arm group label: Regorafenib [B2]
arm group label: Regorafenib [B3]
arm group label: Regorafenib [B4]
arm group label: Regorafenib [B5]
arm group label: Regorafenib [B6]
intervention type: Procedure
intervention name: Sham IVT
description: Sham injections
arm group label: Regorafenib [B1]
arm group label: Regorafenib [B2]
arm group label: Regorafenib [B3]
arm group label: Regorafenib [B4]
arm group label: Regorafenib [B5]
arm group label: Regorafenib [B6]
intervention type: Drug
intervention name: Ranibizumab
description: Subjects receive Ranibizumab as intravitreal injection
arm group label: Ranibizumab
intervention type: Drug
intervention name: Placebo
description: Placebo eye drops
arm group label: Ranibizumab
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Bayer Study Director
role: Study Director
affiliation: Bayer
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country: Australia
country: Austria
country: Canada
country: Chile
country: Colombia
country: Czech Republic
country: France
country: Germany
country: Hong Kong
country: Hungary
country: Israel
country: Italy
country: Japan
country: Korea, Republic of
country: Slovakia
country: Spain
country: Switzerland
country: United States
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: Wet Macular Degeneration
mesh term: Ranibizumab
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: As the study was prematurely terminated since pre-defined proof of concept (PoC) criteria were not met in Part A, hence part B was not initiated. Part B related end points and data were not reported since it is not conducted.
point of contact: 