<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/NCT03294941</url>
  </required_header>
  <id_info>
    <org_study_id>HQ-US-SHUNT-1701</org_study_id>
    <nct_id>NCT03294941</nct_id>
  </id_info>
  <brief_title>The HepQuant SHUNT Test for Monitoring Liver Disease and Treatment Effects by Measuring Liver Function and Physiology</brief_title>
  <official_title>The HepQuant SHUNT Test for Monitoring Liver Disease and Treatment Effects by Measuring Liver Function and Physiology</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>HepQuant, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>HepQuant, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The HepQuant SHUNT test, which is provided as a HepQuant SHUNT Liver Diagnostic Kit, is a&#xD;
      minimally-invasive test of liver function and physiology which has been designated by the FDA&#xD;
      as an investigational drug/device combination product.&#xD;
&#xD;
      Enrollment into one of the 3 Gilead Selonsertib clinical trials (GS-US-416-2124,&#xD;
      GS-US-384-1943/1944) is required for enrollment into the HepQuant study&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The HepQuant study is to run parallel to the Gilead clinical trials,GS-US-416-2124 trial of&#xD;
      Alcoholic Hepatitis, GS-US-384-1943 trial of non-alcoholic steatohepatitis (NASH) fibrosis&#xD;
      Stage 3 (STELLAR-3), and, GS-US-384-1944 trial of NASH and compensated cirrhosis (STELLAR-4).&#xD;
      The time points for the HepQuant SHUNT tests coincide with pre-specified time points within&#xD;
      the Gilead clinical trials. Subjects enrolled in GILEAD's STELLAR and Alcoholic hepatitis&#xD;
      trials may participate concurrently in this HepQuant sponsored investigational device study&#xD;
      at participating US sites only (IDEs as listed above) once approved by the applicable&#xD;
      IRB/IEC.&#xD;
&#xD;
      The main eligibility criteria for enrollment into the HepQuant study is enrollment into one&#xD;
      of the three Gilead clinical trials listed above.&#xD;
&#xD;
      The HepQuant SHUNT Test is minimally-invasive and measures hepatocyte function and inflow to&#xD;
      the liver from the simultaneous clearances (hepatic filtration rates, HFRs) of cholate from&#xD;
      systemic and portal circulations. The Test quantifies portal-systemic shunting (SHUNT) and&#xD;
      generates a liver disease severity index (DSI). DSI is a score from 0 (no disease) to 50&#xD;
      (terminal illness) that is a composite of both HFRs and correlates with stage of fibrosis,&#xD;
      presence of varices, especially large varices, and risk for future clinical outcomes. DSI is&#xD;
      the primary output variable from the HepQuant SHUNT test. The HepQuant SHUNT test potentially&#xD;
      satisfies the unmet medical need for a minimally-invasive test of global liver function and&#xD;
      physiology&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Primary study stopped early&#xD;
  </why_stopped>
  <start_date type="Actual">December 8, 2017</start_date>
  <completion_date type="Actual">September 11, 2019</completion_date>
  <primary_completion_date type="Actual">September 11, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>All subjects receive HepQuant SHUNT test and DSI measurement, but must first be enrolled into one of the three Gilead clinical trials listed above before they can be enrolled in the HepQuant study. Since the assigned intervention, the HepQuant SHUNT test, is the same for all participants in all three Gilead clinical trials, there is only one arm and intervention for the HepQuant study itself. Some analyses are conducted by grouping subjects into those who took the placebo in the parallel drug study versus those who were on active study drug in the parallel study.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Baseline DSI</measure>
    <time_frame>Baseline</time_frame>
    <description>The baseline DSI, or disease severity index, is a measure of severity of liver disease at baseline. The scores for DSI range on a scale from 0 (healthy liver) to 50 (severe liver disease).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in DSI From Baseline to 48 Weeks</measure>
    <time_frame>Baseline and at 48 weeks</time_frame>
    <description>Improvement or worsening of liver disease severity from baseline to the week 48 visit as measured by the change in the disease severity index (DSI) (DSI at 48 weeks minus DSI at baseline). The scores for DSI range on a scale from 0 (healthy liver) to 50 (severe liver disease).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Severity of Liver Disease Index (DSI) Scores Stratified by Baseline NASH CRN Stage of Fibrosis</measure>
    <time_frame>Baseline</time_frame>
    <description>Compared baseline disease severity index (DSI) scores, which are used to measure severity of liver disease on a scale from 0 (healthy liver) to 50 (severe liver disease), between subjects with F3 or F4 Fibrosis at baseline. Fibrosis stages were obtained clinically using the NASH CRN Scoring System to grade liver biopsy results. This scoring system yields scores ranging from F0 (no fibrosis/healthiest) to F4 (cirrhosis/severe disease). Subjects in this study either had F3 Fibrosis (bridging fibrosis) or F4 Fibrosis (cirrhosis), so F3 subjects have less severe disease than F4 subjects.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>NASH - Nonalcoholic Steatohepatitis</condition>
  <arm_group>
    <arm_group_label>HepQuant SHUNT Liver Diagnostic Kit</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>HepQuant SHUNT Liver Diagnostic Kit</intervention_name>
    <description>Serial testing over 48 weeks</description>
    <arm_group_label>HepQuant SHUNT Liver Diagnostic Kit</arm_group_label>
    <other_name>SHUNT test</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        The key inclusion criteria for this HepQuant Parallel Study are the inclusion criteria into&#xD;
        one of the Gilead selonsertib trials (GS-US-416-2124, GS-US-384-1943 or 1944). Once that&#xD;
        has been met, subjects must:&#xD;
&#xD;
          -  Be able to ingest liquid by mouth&#xD;
&#xD;
          -  Have venous access to support a peripheral IV and 6 blood draws&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        The key exclusion criteria for this HepQuant Parallel Study are the exclusion criteria for&#xD;
        one of the Gilead selonsertib trials (GS-US-416-2124, GS-US-384-1943 or 1944). If this has&#xD;
        been met, the subject is not eligible to participate in HepQuant. If no exclusion criteria&#xD;
        has been met for the Gilead selonsertib trial, ADDITIONAL exclusions for HepQuant are:&#xD;
&#xD;
          -  Subject should not have had first dose of selonsertib&#xD;
&#xD;
          -  Subject cannot take anything by mouth&#xD;
&#xD;
          -  Subject cannot be hypersensitive to eggs, albumin preparations, any ingredient in the&#xD;
             formulation, or component of the container&#xD;
&#xD;
          -  Subject cannot have intercurrent medical or surgical illness (eg: acute MI, acute&#xD;
             cerebral hemorrhage, sepsis)&#xD;
&#xD;
          -  subject cannot have had extensive resection of large segments of small intestine&#xD;
             (short gut)&#xD;
&#xD;
          -  Subject cannot have severe gastroparesis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Greg Everson, MD</last_name>
    <role>Study Director</role>
    <affiliation>HepQuant, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Schiff Center for Liver Diseases</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of PA</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Methodist Dallas Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TX Digestive Disease Consultants</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>76092</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Texas Liver Institute</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGuire VA Med Cntr</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washingtion</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>March 30, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 27, 2017</study_first_posted>
  <results_first_submitted>May 3, 2021</results_first_submitted>
  <results_first_submitted_qc>June 24, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 15, 2021</results_first_posted>
  <last_update_submitted>August 5, 2021</last_update_submitted>
  <last_update_submitted_qc>August 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
  </condition_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 15, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT03294941/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study</title>
          <description>All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test&#xD;
HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks</description>
        </group>
        <group group_id="P2">
          <title>HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study</title>
          <description>All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test&#xD;
HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study</title>
          <description>All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test&#xD;
HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks</description>
        </group>
        <group group_id="B2">
          <title>HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study</title>
          <description>All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test&#xD;
HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks</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="4"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="17"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="48.75" lower_limit="28" upper_limit="57"/>
                    <measurement group_id="B2" value="58.15" lower_limit="44" upper_limit="69"/>
                    <measurement group_id="B3" value="55.94" lower_limit="28" upper_limit="69"/>
                  </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="4"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </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="3"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="7"/>
                  </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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Baseline DSI</title>
        <description>The baseline DSI, or disease severity index, is a measure of severity of liver disease at baseline. The scores for DSI range on a scale from 0 (healthy liver) to 50 (severe liver disease).</description>
        <time_frame>Baseline</time_frame>
        <group_list>
          <group group_id="O1">
            <title>HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study</title>
            <description>All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test&#xD;
HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks</description>
          </group>
          <group group_id="O2">
            <title>HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study</title>
            <description>All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test&#xD;
HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Baseline DSI</title>
          <description>The baseline DSI, or disease severity index, is a measure of severity of liver disease at baseline. The scores for DSI range on a scale from 0 (healthy liver) to 50 (severe liver disease).</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.63" spread="3.31"/>
                    <measurement group_id="O2" value="20.93" spread="3.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in DSI From Baseline to 48 Weeks</title>
        <description>Improvement or worsening of liver disease severity from baseline to the week 48 visit as measured by the change in the disease severity index (DSI) (DSI at 48 weeks minus DSI at baseline). The scores for DSI range on a scale from 0 (healthy liver) to 50 (severe liver disease).</description>
        <time_frame>Baseline and at 48 weeks</time_frame>
        <population>15 subjects completed the week 48 SHUNT Test (4 in parallel study placebo group, and 11 in parallel study active study drug group), however, the SHUNT Test samples were unanalyzable for 1 subject on active study drug due to failure of the IV Clearance component of the SHUNT Test. Therefore, the present analysis only includes 14 subjects (4 on placebo, 10 on active study drug).</population>
        <group_list>
          <group group_id="O1">
            <title>HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study</title>
            <description>All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test&#xD;
HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks</description>
          </group>
          <group group_id="O2">
            <title>HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study</title>
            <description>All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test&#xD;
HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change in DSI From Baseline to 48 Weeks</title>
          <description>Improvement or worsening of liver disease severity from baseline to the week 48 visit as measured by the change in the disease severity index (DSI) (DSI at 48 weeks minus DSI at baseline). The scores for DSI range on a scale from 0 (healthy liver) to 50 (severe liver disease).</description>
          <population>15 subjects completed the week 48 SHUNT Test (4 in parallel study placebo group, and 11 in parallel study active study drug group), however, the SHUNT Test samples were unanalyzable for 1 subject on active study drug due to failure of the IV Clearance component of the SHUNT Test. Therefore, the present analysis only includes 14 subjects (4 on placebo, 10 on active study drug).</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.08" spread="2.44"/>
                    <measurement group_id="O2" value="-1.00" spread="2.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Severity of Liver Disease Index (DSI) Scores Stratified by Baseline NASH CRN Stage of Fibrosis</title>
        <description>Compared baseline disease severity index (DSI) scores, which are used to measure severity of liver disease on a scale from 0 (healthy liver) to 50 (severe liver disease), between subjects with F3 or F4 Fibrosis at baseline. Fibrosis stages were obtained clinically using the NASH CRN Scoring System to grade liver biopsy results. This scoring system yields scores ranging from F0 (no fibrosis/healthiest) to F4 (cirrhosis/severe disease). Subjects in this study either had F3 Fibrosis (bridging fibrosis) or F4 Fibrosis (cirrhosis), so F3 subjects have less severe disease than F4 subjects.</description>
        <time_frame>Baseline</time_frame>
        <population>Analysis was conducted to compare DSI scores between Fibrosis categories instead of by placebo vs active study drug groups because the subject numbers were too low. There was only one subject in the placebo group with F4 Fibrosis. Additionally, this outcome measure was established to compare DSI scores to other liver disease severity scores regardless of study drug use, so this analysis was conducted by grouping fibrosis scores.</population>
        <group_list>
          <group group_id="O1">
            <title>HepQuant SHUNT Liver Diagnostic Kit - Subjects With F3 Fibrosis</title>
            <description>All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test&#xD;
HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks</description>
          </group>
          <group group_id="O2">
            <title>HepQuant SHUNT Liver Diagnostic Kit - Subjects With F4 Fibrosis</title>
            <description>All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test&#xD;
HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Severity of Liver Disease Index (DSI) Scores Stratified by Baseline NASH CRN Stage of Fibrosis</title>
          <description>Compared baseline disease severity index (DSI) scores, which are used to measure severity of liver disease on a scale from 0 (healthy liver) to 50 (severe liver disease), between subjects with F3 or F4 Fibrosis at baseline. Fibrosis stages were obtained clinically using the NASH CRN Scoring System to grade liver biopsy results. This scoring system yields scores ranging from F0 (no fibrosis/healthiest) to F4 (cirrhosis/severe disease). Subjects in this study either had F3 Fibrosis (bridging fibrosis) or F4 Fibrosis (cirrhosis), so F3 subjects have less severe disease than F4 subjects.</description>
          <population>Analysis was conducted to compare DSI scores between Fibrosis categories instead of by placebo vs active study drug groups because the subject numbers were too low. There was only one subject in the placebo group with F4 Fibrosis. Additionally, this outcome measure was established to compare DSI scores to other liver disease severity scores regardless of study drug use, so this analysis was conducted by grouping fibrosis scores.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.39" spread="1.70"/>
                    <measurement group_id="O2" value="23.02" spread="3.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months, from the date of enrollment through the 48 week/final study visit.</time_frame>
      <desc>Adverse events are all grouped together because the only intervention in the HepQuant Study is the HepQuant SHUNT Test. Although some analyses are conducted by grouping subjects into those who took the placebo in the parallel drug study versus those who were on active study drug in the parallel study, the HepQuant study itself had only one arm.</desc>
      <group_list>
        <group group_id="E1">
          <title>HepQuant SHUNT Liver Diagnostic Kit</title>
          <description>All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test&#xD;
HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <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="17"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Mild IV-related events</sub_title>
                <description>Mild pain due to IV insertion</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="17"/>
              </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 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>Elyse Handley</name_or_title>
      <organization>HepQuant, LLC</organization>
      <phone>303-923-2109</phone>
      <email>elyse.handley@hepquant.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/NCT03294941
org study id: HQ-US-SHUNT-1701
nct id: NCT03294941
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: Yes
is unapproved device: Yes
The HepQuant SHUNT test, which is provided as a HepQuant SHUNT Liver Diagnostic Kit, is a
      minimally-invasive test of liver function and physiology which has been designated by the FDA
      as an investigational drug/device combination product.

      Enrollment into one of the 3 Gilead Selonsertib clinical trials (GS-US-416-2124,
      GS-US-384-1943/1944) is required for enrollment into the HepQuant study
The HepQuant study is to run parallel to the Gilead clinical trials,GS-US-416-2124 trial of
      Alcoholic Hepatitis, GS-US-384-1943 trial of non-alcoholic steatohepatitis (NASH) fibrosis
      Stage 3 (STELLAR-3), and, GS-US-384-1944 trial of NASH and compensated cirrhosis (STELLAR-4).
      The time points for the HepQuant SHUNT tests coincide with pre-specified time points within
      the Gilead clinical trials. Subjects enrolled in GILEAD's STELLAR and Alcoholic hepatitis
      trials may participate concurrently in this HepQuant sponsored investigational device study
      at participating US sites only (IDEs as listed above) once approved by the applicable
      IRB/IEC.

      The main eligibility criteria for enrollment into the HepQuant study is enrollment into one
      of the three Gilead clinical trials listed above.

      The HepQuant SHUNT Test is minimally-invasive and measures hepatocyte function and inflow to
      the liver from the simultaneous clearances (hepatic filtration rates, HFRs) of cholate from
      systemic and portal circulations. The Test quantifies portal-systemic shunting (SHUNT) and
      generates a liver disease severity index (DSI). DSI is a score from 0 (no disease) to 50
      (terminal illness) that is a composite of both HFRs and correlates with stage of fibrosis,
      presence of varices, especially large varices, and risk for future clinical outcomes. DSI is
      the primary output variable from the HepQuant SHUNT test. The HepQuant SHUNT test potentially
      satisfies the unmet medical need for a minimally-invasive test of global liver function and
      physiology
allocation: N/A
intervention model: Sequential Assignment
intervention model description: All subjects receive HepQuant SHUNT test and DSI measurement, but must first be enrolled into one of the three Gilead clinical trials listed above before they can be enrolled in the HepQuant study. Since the assigned intervention, the HepQuant SHUNT test, is the same for all participants in all three Gilead clinical trials, there is only one arm and intervention for the HepQuant study itself. Some analyses are conducted by grouping subjects into those who took the placebo in the parallel drug study versus those who were on active study drug in the parallel study.
primary purpose: Diagnostic
masking: None (Open Label)
measure: Baseline DSI
time frame: Baseline
description: The baseline DSI, or disease severity index, is a measure of severity of liver disease at baseline. The scores for DSI range on a scale from 0 (healthy liver) to 50 (severe liver disease).
measure: Change in DSI From Baseline to 48 Weeks
time frame: Baseline and at 48 weeks
description: Improvement or worsening of liver disease severity from baseline to the week 48 visit as measured by the change in the disease severity index (DSI) (DSI at 48 weeks minus DSI at baseline). The scores for DSI range on a scale from 0 (healthy liver) to 50 (severe liver disease).
measure: Severity of Liver Disease Index (DSI) Scores Stratified by Baseline NASH CRN Stage of Fibrosis
time frame: Baseline
description: Compared baseline disease severity index (DSI) scores, which are used to measure severity of liver disease on a scale from 0 (healthy liver) to 50 (severe liver disease), between subjects with F3 or F4 Fibrosis at baseline. Fibrosis stages were obtained clinically using the NASH CRN Scoring System to grade liver biopsy results. This scoring system yields scores ranging from F0 (no fibrosis/healthiest) to F4 (cirrhosis/severe disease). Subjects in this study either had F3 Fibrosis (bridging fibrosis) or F4 Fibrosis (cirrhosis), so F3 subjects have less severe disease than F4 subjects.
arm group label: HepQuant SHUNT Liver Diagnostic Kit
arm group type: Other
description: All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test
intervention type: Combination Product
intervention name: HepQuant SHUNT Liver Diagnostic Kit
description: Serial testing over 48 weeks
arm group label: HepQuant SHUNT Liver Diagnostic Kit
other name: SHUNT test
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Greg Everson, MD
role: Study Director
affiliation: HepQuant, LLC
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 