<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/NCT03812328</url>
  </required_header>
  <id_info>
    <org_study_id>SELK2-00005</org_study_id>
    <secondary_id>2018-003122-88</secondary_id>
    <nct_id>NCT03812328</nct_id>
  </id_info>
  <brief_title>Study to Assess the Safety and Efficacy of SelK2 to Prevent Blood Clots in Patients Undergoing Total Knee Replacement</brief_title>
  <acronym>COURSE</acronym>
  <official_title>A Phase 2, Randomized, Active Comparator-Controlled, Open-Label, Adaptive Design Study to Assess the Safety and Efficacy of Intravenously-Administered SelK2 in Patients Undergoing Total Knee Arthroplasty</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tetherex Pharmaceuticals Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tetherex Pharmaceuticals Corporation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to determine if an investigational medication called SelK2&#xD;
      works in preventing a condition called &quot;venous thromboembolism&quot; (VTE) in patients having a&#xD;
      total knee replacement. SelK2 has been designed to attach to a protein found on blood cells&#xD;
      and blood vessels. By attaching to this protein, SelK2 is designed to decrease the&#xD;
      inflammatory process in the blood vessel wall that leads to the formation of blood clots in&#xD;
      the vessel (called thrombosis). By decreasing the inflammatory process, SelK2 may reduce the&#xD;
      risk of VTE following joint replacement surgery. In addition, because SelK2 is not a blood&#xD;
      thinner, it is expected that the risk for bleeding will also be reduced.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 20, 2019</start_date>
  <completion_date type="Actual">November 14, 2019</completion_date>
  <primary_completion_date type="Actual">October 1, 2019</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>
    <intervention_model_description>This was an adaptive design study. The first two arms of the study enrolled patients in a 1:1 ratio to receive either SelK2 or an active comparator. The adaptive arm (SelK2 plus active comparator) was initiated at the discretion of the Steering and Safety Committee. The study then enrolled patients in a 2:1 ratio to receive either SelK2 with an active comparator or an active comparator only.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Total Venous Thromboembolism</measure>
    <time_frame>10 ± 2 Days After Total Knee Replacement</time_frame>
    <description>The primary efficacy endpoint was incidence of total VTE (reported as a percentage of patients) during the Treatment Phase up to venography day (10 ± 2 days after total knee replacement). All efficacy endpoint data was adjudicated by the blinded Central Independent Adjudication Committee (CIAC).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Major or Clinically Relevant Non-major Bleeding Events</measure>
    <time_frame>10 ± 2 Days After Total Knee Replacement</time_frame>
    <description>All suspected bleeding events were reviewed by the Central Independent Adjudication Committee (CIAC) in a blinded fashion and were adjudicated for categorization as Major Bleeding (MB), Clinically Relevant Non-Major Bleeding (CRNMB), Minor Bleeding, or combination of MB and CRNMB. The outcome measure assessed the incidence of MB or CRNMB.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">207</enrollment>
  <condition>Venous Thromboembolism</condition>
  <arm_group>
    <arm_group_label>SelK2 and Enoxaparin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>I.V., single-dose (SelK2) and SC, QD for up to 10 ± 2 days (Enoxaparin)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Enoxaparin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>SC, QD for up to 10 ± 2 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SelK2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>I.V., single-dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SelK2</intervention_name>
    <description>I.V., single-dose</description>
    <arm_group_label>SelK2</arm_group_label>
    <arm_group_label>SelK2 and Enoxaparin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Enoxaparin</intervention_name>
    <description>SC, QD for up to 10 ± 2 days</description>
    <arm_group_label>Enoxaparin</arm_group_label>
    <arm_group_label>SelK2 and Enoxaparin</arm_group_label>
    <other_name>Lovenox</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Males or females, 18-80 years of age (inclusive)&#xD;
&#xD;
          -  Planned to undergo elective, primary total unilateral Total Knee Arthroplasty under&#xD;
             general anesthesia&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Previous deep vein thrombosis (DVT) of the leg or pulmonary embolism (PE) within the&#xD;
             past year&#xD;
&#xD;
          -  Any underlying condition (e.g., atrial fibrillation, mechanical heart valve, or recent&#xD;
             pulmonary embolism) that may lead to the required concomitant use of&#xD;
             anticoagulants/antiplatelet agents (e.g., warfarin, dabigatran, rivaroxaban, apixaban,&#xD;
             clopidogrel) that may affect study outcome or any other drug influencing coagulation&#xD;
             (except low dose aspirin (100 mg or less))&#xD;
&#xD;
          -  Anticipated use of intermittent pneumatic compression devices and/or&#xD;
             electrical/mechanical muscle stimulators post Total Knee Arthroplasty procedure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Russell Rother, Ph.D.</last_name>
    <role>Study Director</role>
    <affiliation>Tetherex Pharmaceuticals Corporation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UMHAT Kanev AD</name>
      <address>
        <city>Ruse</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Acibadem City Clinic Tokuda Hospital EAD</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMHAT Tsaritsa Yoanna - ISUL</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Hospital of Liepaja</name>
      <address>
        <city>Liepāja</city>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital of Traumatology and Orthopaedics</name>
      <address>
        <city>Riga</city>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ORTO Clinic</name>
      <address>
        <city>Riga</city>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riga's 2nd Hospital</name>
      <address>
        <city>Riga</city>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vidzemes Hospital</name>
      <address>
        <city>Valmiera</city>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaunas Clinical Hospital</name>
      <address>
        <city>Kaunas</city>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klaipeda University Hospital</name>
      <address>
        <city>Klaipeda</city>
        <country>Lithuania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Kliniczny w Białymstoku</name>
      <address>
        <city>Białystok</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samodzielny Publiczny Zakład Opieki Zdrowotnej</name>
      <address>
        <city>Bielsk Podlaski</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Ogólny im. dr Witolda Ginela w Grajewie</name>
      <address>
        <city>Grajewo</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie</name>
      <address>
        <city>Kraków</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojewódzki Szpital Specjalistyczny</name>
      <address>
        <city>Lublin</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego</name>
      <address>
        <city>Wrocław</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi</name>
      <address>
        <city>Łódź</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Nonprofit Enterprise Cherkasy Regional Hospital of Cherkasy Oblast Council</name>
      <address>
        <city>Cherkasy</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center of Traumatology &amp; Orthopedics</name>
      <address>
        <city>Chernivtsi</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ivano-Frankivsk Regional Clinical Hospital</name>
      <address>
        <city>Ivano-Frankivs'k</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kiev Regional Clinical Hospital</name>
      <address>
        <city>Kiev</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Latvia</country>
    <country>Lithuania</country>
    <country>Poland</country>
    <country>Ukraine</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <results_first_submitted>October 30, 2020</results_first_submitted>
  <results_first_submitted_qc>October 30, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 24, 2020</results_first_posted>
  <last_update_submitted>December 14, 2020</last_update_submitted>
  <last_update_submitted_qc>December 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>venous thromboembolism</keyword>
  <keyword>adhesion molecule</keyword>
  <keyword>P-selectin glycoprotein ligand 1</keyword>
  <keyword>P-selectin</keyword>
  <keyword>venous thrombosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Venous Thromboembolism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enoxaparin</mesh_term>
  </intervention_browse>
  <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, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03812328/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>SelK2</title>
          <description>I.V., single-dose</description>
        </group>
        <group group_id="P2">
          <title>SelK2 and Enoxaparin</title>
          <description>I.V., single-dose (SelK2) and SC, QD for up to 10 ± 2 days (Enoxaparin)</description>
        </group>
        <group group_id="P3">
          <title>Enoxaparin</title>
          <description>QD for up to 10 ± 2 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="55"/>
                <participants group_id="P2" count="63"/>
                <participants group_id="P3" count="89"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Modified Intent-to-Treat (mITT) Population</title>
              <participants_list>
                <participants group_id="P1" count="48"/>
                <participants group_id="P2" count="61"/>
                <participants group_id="P3" count="84"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Population</title>
              <participants_list>
                <participants group_id="P1" count="55"/>
                <participants group_id="P2" count="63"/>
                <participants group_id="P3" count="88"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="55"/>
                <participants group_id="P2" count="60"/>
                <participants group_id="P3" count="88"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>SelK2</title>
          <description>I.V., single-dose</description>
        </group>
        <group group_id="B2">
          <title>SelK2 and Enoxaparin</title>
          <description>I.V., single-dose (SelK2) and SC, QD for up to 10 ± 2 days (Enoxaparin)&#xD;
SelK2: I.V., single-dose&#xD;
Enoxaparin: SC, QD for up to 10 ± 2 days</description>
        </group>
        <group group_id="B3">
          <title>Enoxaparin</title>
          <description>SC, QD for up to 10 ± 2 days&#xD;
Enoxaparin: SC, QD for up to 10 ± 2 days</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="55"/>
            <count group_id="B2" value="63"/>
            <count group_id="B3" value="89"/>
            <count group_id="B4" value="207"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="33"/>
                    <measurement group_id="B4" value="78"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="56"/>
                    <measurement group_id="B4" value="129"/>
                  </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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66.3" spread="6.35"/>
                    <measurement group_id="B2" value="66.3" spread="7.54"/>
                    <measurement group_id="B3" value="65.6" spread="7.30"/>
                    <measurement group_id="B4" value="66.0" spread="7.11"/>
                  </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="42"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="68"/>
                    <measurement group_id="B4" value="162"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="21"/>
                    <measurement group_id="B4" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="88"/>
                    <measurement group_id="B4" value="205"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="89"/>
                    <measurement group_id="B4" value="207"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" 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>Latvia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="30"/>
                    <measurement group_id="B4" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ukraine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="27"/>
                    <measurement group_id="B4" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poland</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lithuania</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bulgaria</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Total Venous Thromboembolism</title>
        <description>The primary efficacy endpoint was incidence of total VTE (reported as a percentage of patients) during the Treatment Phase up to venography day (10 ± 2 days after total knee replacement). All efficacy endpoint data was adjudicated by the blinded Central Independent Adjudication Committee (CIAC).</description>
        <time_frame>10 ± 2 Days After Total Knee Replacement</time_frame>
        <population>Analysis was performed on the modified intent-to-treat (mITT) population consisting of all randomized patients who also had a successful venogram or symptomatic VTE event, which allowed for assessment of the primary efficacy outcome.</population>
        <group_list>
          <group group_id="O1">
            <title>SelK2</title>
            <description>I.V., single-dose</description>
          </group>
          <group group_id="O2">
            <title>SelK2 and Enoxaparin</title>
            <description>I.V., single-dose (SelK2) and SC, QD for up to 10 ± 2 days (Enoxaparin)&#xD;
SelK2: I.V., single-dose&#xD;
Enoxaparin: SC, QD for up to 10 ± 2 days</description>
          </group>
          <group group_id="O3">
            <title>Enoxaparin</title>
            <description>SC, QD for up to 10 ± 2 days&#xD;
Enoxaparin: SC, QD for up to 10 ± 2 days</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Total Venous Thromboembolism</title>
          <description>The primary efficacy endpoint was incidence of total VTE (reported as a percentage of patients) during the Treatment Phase up to venography day (10 ± 2 days after total knee replacement). All efficacy endpoint data was adjudicated by the blinded Central Independent Adjudication Committee (CIAC).</description>
          <population>Analysis was performed on the modified intent-to-treat (mITT) population consisting of all randomized patients who also had a successful venogram or symptomatic VTE event, which allowed for assessment of the primary efficacy outcome.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="48"/>
                <count group_id="O2" value="61"/>
                <count group_id="O3" value="84"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="29"/>
                    <measurement group_id="O3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Major or Clinically Relevant Non-major Bleeding Events</title>
        <description>All suspected bleeding events were reviewed by the Central Independent Adjudication Committee (CIAC) in a blinded fashion and were adjudicated for categorization as Major Bleeding (MB), Clinically Relevant Non-Major Bleeding (CRNMB), Minor Bleeding, or combination of MB and CRNMB. The outcome measure assessed the incidence of MB or CRNMB.</description>
        <time_frame>10 ± 2 Days After Total Knee Replacement</time_frame>
        <population>Analysis was performed on the safety population consisting of all patients who received at least 1 dose of study drug, analyzed by actual treatment received.</population>
        <group_list>
          <group group_id="O1">
            <title>SelK2</title>
            <description>I.V., single-dose</description>
          </group>
          <group group_id="O2">
            <title>SelK2 and Enoxaparin</title>
            <description>I.V., single-dose (SelK2) and SC, QD for up to 10 ± 2 days (Enoxaparin)&#xD;
SelK2: I.V., single-dose&#xD;
Enoxaparin: SC, QD for up to 10 ± 2 days</description>
          </group>
          <group group_id="O3">
            <title>Enoxaparin</title>
            <description>SC, QD for up to 10 ± 2 days&#xD;
Enoxaparin: SC, QD for up to 10 ± 2 days</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Major or Clinically Relevant Non-major Bleeding Events</title>
          <description>All suspected bleeding events were reviewed by the Central Independent Adjudication Committee (CIAC) in a blinded fashion and were adjudicated for categorization as Major Bleeding (MB), Clinically Relevant Non-Major Bleeding (CRNMB), Minor Bleeding, or combination of MB and CRNMB. The outcome measure assessed the incidence of MB or CRNMB.</description>
          <population>Analysis was performed on the safety population consisting of all patients who received at least 1 dose of study drug, analyzed by actual treatment received.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="55"/>
                <count group_id="O2" value="63"/>
                <count group_id="O3" value="88"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Through Day 57</time_frame>
      <group_list>
        <group group_id="E1">
          <title>SelK2</title>
          <description>I.V., single-dose</description>
        </group>
        <group group_id="E2">
          <title>SelK2 and Enoxaparin</title>
          <description>I.V., single-dose (SelK2) and SC, QD for up to 10 ± 2 days (Enoxaparin)&#xD;
SelK2: I.V., single-dose&#xD;
Enoxaparin: SC, QD for up to 10 ± 2 days</description>
        </group>
        <group group_id="E3">
          <title>Enoxaparin</title>
          <description>SC, QD for up to 10 ± 2 days&#xD;
Enoxaparin: SC, QD for up to 10 ± 2 days</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21.1</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="55"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="88"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="55"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="63"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial ischaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Post procedural infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="55"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="88"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA 21.1</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="9" subjects_at_risk="55"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="63"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural haemorrhage</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="55"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="63"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="88"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="63"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="88"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="55"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="63"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="55"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="88"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="55"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="88"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Jonathan Stocker, Ph.D.</name_or_title>
      <organization>Tetherex Pharmaceuticals</organization>
      <phone>855-222-0722</phone>
      <email>jstocker@tetherex.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/NCT03812328
org study id: SELK2-00005
secondary id: 2018-003122-88
nct id: NCT03812328
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The main purpose of this study is to determine if an investigational medication called SelK2
      works in preventing a condition called "venous thromboembolism" (VTE) in patients having a
      total knee replacement. SelK2 has been designed to attach to a protein found on blood cells
      and blood vessels. By attaching to this protein, SelK2 is designed to decrease the
      inflammatory process in the blood vessel wall that leads to the formation of blood clots in
      the vessel (called thrombosis). By decreasing the inflammatory process, SelK2 may reduce the
      risk of VTE following joint replacement surgery. In addition, because SelK2 is not a blood
      thinner, it is expected that the risk for bleeding will also be reduced.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This was an adaptive design study. The first two arms of the study enrolled patients in a 1:1 ratio to receive either SelK2 or an active comparator. The adaptive arm (SelK2 plus active comparator) was initiated at the discretion of the Steering and Safety Committee. The study then enrolled patients in a 2:1 ratio to receive either SelK2 with an active comparator or an active comparator only.
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: Percentage of Participants With Total Venous Thromboembolism
time frame: 10 ± 2 Days After Total Knee Replacement
description: The primary efficacy endpoint was incidence of total VTE (reported as a percentage of patients) during the Treatment Phase up to venography day (10 ± 2 days after total knee replacement). All efficacy endpoint data was adjudicated by the blinded Central Independent Adjudication Committee (CIAC).
measure: Percentage of Participants With Major or Clinically Relevant Non-major Bleeding Events
time frame: 10 ± 2 Days After Total Knee Replacement
description: All suspected bleeding events were reviewed by the Central Independent Adjudication Committee (CIAC) in a blinded fashion and were adjudicated for categorization as Major Bleeding (MB), Clinically Relevant Non-Major Bleeding (CRNMB), Minor Bleeding, or combination of MB and CRNMB. The outcome measure assessed the incidence of MB or CRNMB.
arm group label: SelK2 and Enoxaparin
arm group type: Experimental
description: I.V., single-dose (SelK2) and SC, QD for up to 10 ± 2 days (Enoxaparin)
arm group label: Enoxaparin
arm group type: Active Comparator
description: SC, QD for up to 10 ± 2 days
arm group label: SelK2
arm group type: Experimental
description: I.V., single-dose
intervention type: Drug
intervention name: SelK2
description: I.V., single-dose
arm group label: SelK2
arm group label: SelK2 and Enoxaparin
intervention type: Biological
intervention name: Enoxaparin
description: SC, QD for up to 10 ± 2 days
arm group label: Enoxaparin
arm group label: SelK2 and Enoxaparin
other name: Lovenox
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Russell Rother, Ph.D.
role: Study Director
affiliation: Tetherex Pharmaceuticals Corporation
facility: 
facility: 
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country: Bulgaria
country: Latvia
country: Lithuania
country: Poland
country: Ukraine
responsible party type: Sponsor
mesh term: Thromboembolism
mesh term: Venous Thromboembolism
mesh term: Enoxaparin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 