<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/NCT03772665</url>
  </required_header>
  <id_info>
    <org_study_id>4429-301</org_study_id>
    <secondary_id>R01FD006849</secondary_id>
    <nct_id>NCT03772665</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Emixustat in Stargardt Disease</brief_title>
  <acronym>SeaSTAR</acronym>
  <official_title>A Phase 3 Multicenter, Randomized, Double-Masked Study Comparing the Efficacy and Safety of Emixustat Hydrochloride With Placebo for the Treatment of Macular Atrophy Secondary to Stargardt Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kubota Vision Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Food and Drug Administration (FDA)</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Kubota Vision Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if emixustat hydrochloride reduces the rate of&#xD;
      progression of macular atrophy compared to placebo in subjects with Stargardt disease.&#xD;
&#xD;
      Funding Source -- FDA OOPD&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Stargardt disease is a rare, inherited degenerative disease of the retina affecting&#xD;
      approximately 1 in 8000 to 10 000 people and is the most common type of hereditary macular&#xD;
      dystrophy. There are no approved treatments for STGD. This disease is characterized by an&#xD;
      excessive accumulation of lipofuscin at the level of the retinal pigment epithelium (RPE).&#xD;
      Lipofuscin is made of lipids, proteins, and toxic bis retinoids (such as N retinylidene N&#xD;
      retinylethanolamine [A2E]). Accumulation of the toxic bis retinoids found in lipofuscin is&#xD;
      thought to cause RPE cell dysfunction and eventual apoptosis, resulting in photoreceptor&#xD;
      death and loss of vision.&#xD;
&#xD;
      Stargardt disease has several sub types, where autosomal recessive STGD (STGD1) accounts for&#xD;
      the majority (&gt;95%) of all cases. STGD1 is typically diagnosed in the first 3 decades of life&#xD;
      and is caused by mutations of the adenosine triphosphate binding cassette subfamily A member&#xD;
      4 (ABCA4) gene. The ABCA4 gene product transports N retinylidene phosphatidylethanolamine (a&#xD;
      precursor of toxic bis retinoids) from the lumen side of photoreceptor disc membranes to the&#xD;
      cytoplasmic side where the retinal is hydrolyzed from phosphatidylethanolamine. Mutations of&#xD;
      the ABCA4 gene result in accumulation of this precursor in disc membranes that are eventually&#xD;
      phagocytized by RPE cells, where the precursors are converted into toxic bis retinoids such&#xD;
      as A2E. In addition to being a precursor to A2E, all trans retinal has also been implicated&#xD;
      in the pathogenesis of STGD through its role in light-mediated toxicity.&#xD;
&#xD;
      Emixustat hydrochloride (emixustat) has been developed by Acucela Inc. for retinal diseases&#xD;
      including Stargardt disease (STGD). Emixustat is a potent inhibitor of RPE65 isomerization&#xD;
      activity and reduces visual chromophore (11 cis retinal) production in a dose-dependent and&#xD;
      reversible manner. Because 11 cis-retinal and its photoproduct (all trans retinal) are&#xD;
      substrates for biosynthesis of retinoid toxins (eg, A2E), chronic treatment with emixustat&#xD;
      retards the rate at which these toxins accumulate.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 7, 2018</start_date>
  <completion_date type="Actual">June 23, 2022</completion_date>
  <primary_completion_date type="Actual">June 13, 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>
    <intervention_model_description>This is a multicenter, randomized, double-masked, placebo-controlled study to evaluate the efficacy and safety of emixustat compared to placebo in subjects who have Macular Atrophy secondary to Stargardt disease.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-Masked</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Rate of Change in Total Area of Macular Atrophy, as Measured by Fundus Autofluorescence (FAF)</measure>
    <time_frame>24 months</time_frame>
    <description>Mean rate of change in total area of macular atrophy, as measured by fundus autofluorescence (FAF)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">194</enrollment>
  <condition>Stargardt Disease</condition>
  <arm_group>
    <arm_group_label>Emixustat</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Includes identical tablets with only inactive ingredients (0 mg).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Emixustat</intervention_name>
    <description>Once daily oral tablet taken for 24 months</description>
    <arm_group_label>Emixustat</arm_group_label>
    <other_name>emixustat hydrochloride</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Once daily oral tablet taken for 24 months</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A clinical diagnosis of macular atrophy secondary to Stargardt disease (STGD)&#xD;
&#xD;
          -  Macular atrophy measured to fall within a defined size range&#xD;
&#xD;
          -  Two mutations of the ABCA4 gene. If only one mutation, a typical STGD appearance of&#xD;
             the retina.&#xD;
&#xD;
          -  Visual acuity in the study eye of at least 20/320&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Macular atrophy secondary to a disease other than STGD&#xD;
&#xD;
          -  Mutations of genes, other than ABCA4, that are associated with retinal degeneration&#xD;
&#xD;
          -  Surgery in the study eye in the past 3 months&#xD;
&#xD;
          -  Prior participation in a gene therapy or stem cell clinical trial for STGD&#xD;
&#xD;
          -  Recent participation in a clinical trial for STGD evaluating a complement inhibitor or&#xD;
             vitamin A derivative&#xD;
&#xD;
          -  Use of certain medications in the past 4 weeks that might interfere with emixustat&#xD;
&#xD;
          -  An abnormal electrocardiogram (ECG)&#xD;
&#xD;
          -  Certain abnormalities on laboratory blood testing&#xD;
&#xD;
          -  Female subjects who are pregnant or nursing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeff Gregory, MD</last_name>
    <role>Study Director</role>
    <affiliation>VP of Clinical Development, Acucela</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Retina-Vitreous Associates Medical Group</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Dept. of Ophthalmology</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143-0730</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Wilmer Eye Institute Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Kellogg Eye Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Eye Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Casey Eye Institute - OHSU</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Foundation of the Southwest</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah John Moran Eye Center</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin-Eye Institute</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Santa Casa de Misericórdia de Belo Horizonte</name>
      <address>
        <city>Belo Horizonte</city>
        <state>Minas Gerais</state>
        <zip>30150-320</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sao Paulo</name>
      <address>
        <city>São Paulo</city>
        <zip>04024-002</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>MSG 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet-Glostrup</name>
      <address>
        <city>Glostrup</city>
        <state>Hovedstaden</state>
        <zip>DK-2600</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Service D'Ophtalmologie Chi Creteil</name>
      <address>
        <city>Créteil</city>
        <state>Île-de-France</state>
        <zip>94000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHNO Quinze-Vingts - CIC</name>
      <address>
        <city>Paris</city>
        <state>Île-de-France</state>
        <zip>75012</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Tübingen, Department für Augenheilkunde</name>
      <address>
        <city>Tübingen</city>
        <state>Baden-Württemberg</state>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitäts-Augenklinik Bonn</name>
      <address>
        <city>Bonn</city>
        <zip>53127</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOU Università della Campania Luigi Vanvitelli</name>
      <address>
        <city>Naples</city>
        <state>Campania</state>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Università Cattolica del Sacro Cuore - Fondazione Policlinico Gemelli</name>
      <address>
        <city>Rome</city>
        <state>Lazio</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Ospedale San Raffaele</name>
      <address>
        <city>Milan</city>
        <state>Lombardy</state>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UOC Oculistica Asst Fatebene Pratelli Sacco Universita delgi Studi di Milano</name>
      <address>
        <city>Milan</city>
        <state>Lombardy</state>
        <zip>20157</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SODC di Oculistica AOU Careggi</name>
      <address>
        <city>Florence</city>
        <state>Tuscany</state>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radboud University Medical Center</name>
      <address>
        <city>Nijmegen</city>
        <state>Gelderland</state>
        <zip>6500</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pretoria Eye Institute</name>
      <address>
        <city>Pretoria</city>
        <state>Gauteng</state>
        <zip>0082</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Jimenez Diaz University Hospital</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oxford Eye Hospital,Oxford University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Oxford</city>
        <state>Oxfordshire</state>
        <zip>OXD3 9DU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moorfields Eye Hospital NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>EC1V 2PD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Canada</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>November 30, 2018</study_first_submitted>
  <study_first_submitted_qc>December 9, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <results_first_submitted>July 13, 2023</results_first_submitted>
  <results_first_submitted_qc>July 13, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">August 3, 2023</results_first_posted>
  <last_update_submitted>July 13, 2023</last_update_submitted>
  <last_update_submitted_qc>July 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Stargardt Disease</keyword>
  <keyword>STGD</keyword>
  <keyword>ABCA4</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stargardt Disease</mesh_term>
    <mesh_term>Macular Degeneration</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 21, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03772665/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Emixustat</title>
          <description>10 mg&#xD;
Emixustat: Once daily oral tablet taken for 24 months</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Includes identical tablets with only inactive ingredients (0 mg).&#xD;
Placebo: Once daily oral tablet taken for 24 months</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="128"/>
                <participants group_id="P2" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="127"/>
                <participants group_id="P2" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>ITT</population>
      <group_list>
        <group group_id="B1">
          <title>Emixustat</title>
          <description>10 mg&#xD;
Emixustat: Once daily oral tablet taken for 24 months</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Includes identical tablets with only inactive ingredients (0 mg).&#xD;
Placebo: Once daily oral tablet taken for 24 months</description>
        </group>
        <group group_id="B3">
          <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="128"/>
            <count group_id="B2" value="66"/>
            <count group_id="B3" value="194"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="122"/>
                    <measurement group_id="B2" value="64"/>
                    <measurement group_id="B3" value="186"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43.9" spread="15.03"/>
                    <measurement group_id="B2" value="43.0" spread="14.07"/>
                    <measurement group_id="B3" value="43.6" spread="14.75"/>
                  </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="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="59"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="88"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="69"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="106"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <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="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Netherlands</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Brazil</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Denmark</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>South Africa</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>France</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="128"/>
                    <count group_id="B2" value="66"/>
                    <count group_id="B3" value="194"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Rate of Change in Total Area of Macular Atrophy, as Measured by Fundus Autofluorescence (FAF)</title>
        <description>Mean rate of change in total area of macular atrophy, as measured by fundus autofluorescence (FAF)</description>
        <time_frame>24 months</time_frame>
        <population>ITT</population>
        <group_list>
          <group group_id="O1">
            <title>Emixustat</title>
            <description>10 mg&#xD;
Emixustat: Once daily oral tablet taken for 24 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Includes identical tablets with only inactive ingredients (0 mg).&#xD;
Placebo: Once daily oral tablet taken for 24 months</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Rate of Change in Total Area of Macular Atrophy, as Measured by Fundus Autofluorescence (FAF)</title>
          <description>Mean rate of change in total area of macular atrophy, as measured by fundus autofluorescence (FAF)</description>
          <population>ITT</population>
          <units>Rate of change from BL (mm^2/yr)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="128"/>
                <count group_id="O2" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.280" spread="0.0783"/>
                    <measurement group_id="O2" value="1.309" spread="0.1002"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 months</time_frame>
      <desc>MedDRA version 25.0</desc>
      <group_list>
        <group group_id="E1">
          <title>Emixustat</title>
          <description>10 mg&#xD;
Emixustat: Once daily oral tablet taken for 24 months</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Includes identical tablets with only inactive ingredients (0 mg).&#xD;
Placebo: Once daily oral tablet taken for 24 months</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 25.0</default_vocab>
        <default_assessment>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="0" subjects_at_risk="127"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="127"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>agina pectoris</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="66"/>
              </event>
              <event>
                <sub_title>atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Visual disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury, posioning and procedural</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>neoplasm</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="127"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous system disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Vascular disorder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 25.0</default_vocab>
        <default_assessment>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="1" subjects_at_risk="127"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Visual acuity reduced</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="127"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="66"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Jeff Gregory</name_or_title>
      <organization>Acucela, dba Kubota Vision</organization>
      <phone>2068058310</phone>
      <email>clinicaltrials@acucela.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/NCT03772665
org study id: 4429-301
secondary id: R01FD006849
nct id: NCT03772665
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine if emixustat hydrochloride reduces the rate of
      progression of macular atrophy compared to placebo in subjects with Stargardt disease.

      Funding Source -- FDA OOPD
Stargardt disease is a rare, inherited degenerative disease of the retina affecting
      approximately 1 in 8000 to 10 000 people and is the most common type of hereditary macular
      dystrophy. There are no approved treatments for STGD. This disease is characterized by an
      excessive accumulation of lipofuscin at the level of the retinal pigment epithelium (RPE).
      Lipofuscin is made of lipids, proteins, and toxic bis retinoids (such as N retinylidene N
      retinylethanolamine [A2E]). Accumulation of the toxic bis retinoids found in lipofuscin is
      thought to cause RPE cell dysfunction and eventual apoptosis, resulting in photoreceptor
      death and loss of vision.

      Stargardt disease has several sub types, where autosomal recessive STGD (STGD1) accounts for
      the majority (>95%) of all cases. STGD1 is typically diagnosed in the first 3 decades of life
      and is caused by mutations of the adenosine triphosphate binding cassette subfamily A member
      4 (ABCA4) gene. The ABCA4 gene product transports N retinylidene phosphatidylethanolamine (a
      precursor of toxic bis retinoids) from the lumen side of photoreceptor disc membranes to the
      cytoplasmic side where the retinal is hydrolyzed from phosphatidylethanolamine. Mutations of
      the ABCA4 gene result in accumulation of this precursor in disc membranes that are eventually
      phagocytized by RPE cells, where the precursors are converted into toxic bis retinoids such
      as A2E. In addition to being a precursor to A2E, all trans retinal has also been implicated
      in the pathogenesis of STGD through its role in light-mediated toxicity.

      Emixustat hydrochloride (emixustat) has been developed by Acucela Inc. for retinal diseases
      including Stargardt disease (STGD). Emixustat is a potent inhibitor of RPE65 isomerization
      activity and reduces visual chromophore (11 cis retinal) production in a dose-dependent and
      reversible manner. Because 11 cis-retinal and its photoproduct (all trans retinal) are
      substrates for biosynthesis of retinoid toxins (eg, A2E), chronic treatment with emixustat
      retards the rate at which these toxins accumulate.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a multicenter, randomized, double-masked, placebo-controlled study to evaluate the efficacy and safety of emixustat compared to placebo in subjects who have Macular Atrophy secondary to Stargardt disease.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-Masked
measure: Mean Rate of Change in Total Area of Macular Atrophy, as Measured by Fundus Autofluorescence (FAF)
time frame: 24 months
description: Mean rate of change in total area of macular atrophy, as measured by fundus autofluorescence (FAF)
arm group label: Emixustat
arm group type: Experimental
description: 10 mg
arm group label: Placebo
arm group type: Placebo Comparator
description: Includes identical tablets with only inactive ingredients (0 mg).
intervention type: Drug
intervention name: Emixustat
description: Once daily oral tablet taken for 24 months
arm group label: Emixustat
other name: emixustat hydrochloride
intervention type: Drug
intervention name: Placebo
description: Once daily oral tablet taken for 24 months
arm group label: Placebo
criteria: 
gender: All
minimum age: 16 Years
maximum age: N/A
healthy volunteers: No
last name: Jeff Gregory, MD
role: Study Director
affiliation: VP of Clinical Development, Acucela
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Brazil
country: Canada
country: Denmark
country: France
country: Germany
country: Italy
country: Netherlands
country: South Africa
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Stargardt Disease
mesh term: Macular Degeneration
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 