<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/NCT01707472</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-321-0107</org_study_id>
    <nct_id>NCT01707472</nct_id>
  </id_info>
  <brief_title>Study of Simtuzumab in HIV and/or Hepatitis C- Infected Adults With Liver Fibrosis</brief_title>
  <official_title>A Phase 2a Study of an Anti-LOXL2 Monoclonal Antibody (GS-6624) in HIV and/or Hepatitis C- Infected Subjects With Liver Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Gilead Sciences</source>
  <oversight_info>
    <has_dmc>No</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 primary objective of this study is to assess the safety and tolerability of simtuzumab&#xD;
      (formerly GS-6624) in HIV and/or hepatitis C virus (HCV)-infected adults with evidence of&#xD;
      liver fibrosis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 4, 2012</start_date>
  <completion_date type="Actual">October 17, 2014</completion_date>
  <primary_completion_date type="Actual">October 17, 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Experiencing Treatment-Emergent Adverse Events</measure>
    <time_frame>First dose date up to Week 24 plus 30 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24</measure>
    <time_frame>Baseline; Week 24</time_frame>
    <description>The Ishak fibrosis score measures the degree of liver fibrosis (scarring) and ranges from 0 (best) to 6 (worst). A negative value in change from baseline indicates an improvement and a positive value indicates worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in HVPG at Week 24</measure>
    <time_frame>Baseline; Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in MQC at Week 24</measure>
    <time_frame>Baseline; Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Alpha SMA at Week 24</measure>
    <time_frame>Baseline; Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24</measure>
    <time_frame>Baseline; Week 24</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Liver Fibrosis</condition>
  <condition>Hepatitis C</condition>
  <condition>HIV</condition>
  <condition>HIV/HCV Co-infection</condition>
  <arm_group>
    <arm_group_label>Simtuzumab in HIV Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Simtuzumab in HCV Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HCV-infected participants will receive simtuzumab every 2 weeks for 24 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Simtuzumab in HIV/HCV Co-Infected Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV/HCV co-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Simtuzumab</intervention_name>
    <description>700 mg intravenously for a total of 12 infusions.</description>
    <arm_group_label>Simtuzumab in HCV Patients</arm_group_label>
    <arm_group_label>Simtuzumab in HIV Patients</arm_group_label>
    <arm_group_label>Simtuzumab in HIV/HCV Co-Infected Patients</arm_group_label>
    <other_name>Anti-LOXL2 Monoclonal Antibody</other_name>
    <other_name>GS-6624</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  HIV-infected individuals must have positive serologies with viral load suppressed&#xD;
             below 400 copies/mL&#xD;
&#xD;
          -  HCV-infected individuals must have:&#xD;
&#xD;
               -  Chronic HCV infection with HCV RNA ≥ 2000 IU/ml AND at least 1 of the following:&#xD;
&#xD;
               -  Been null responder to previous pegylated interferon and ribavirin therapy OR&#xD;
&#xD;
               -  Failed to achieve sustained virologic response (SVR) on a regimen containing a&#xD;
                  direct-acting antiviral (DAA) in addition to pegylated interferon and ribavirin&#xD;
                  OR&#xD;
&#xD;
               -  Are unwilling to receive or have contraindications to interferon therapy for HCV&#xD;
&#xD;
          -  HIV/HCV co-infected individuals must have:&#xD;
&#xD;
               -  Positive HIV serologies with viral load suppressed below 400 copies/mL&#xD;
&#xD;
               -  Chronic HCV infection with HCV RNA ≥ 2000 IU/ml AND at least 1 of the following:&#xD;
&#xD;
               -  Been null responder to previous pegylated interferon and ribavirin therapy OR&#xD;
&#xD;
               -  Failed to achieve SVR on a regimen containing a direct-acting antiviral (DAA) in&#xD;
                  addition to pegylated interferon and ribavirin OR&#xD;
&#xD;
               -  Are unwilling to receive or have contraindications to interferon therapy for HCV&#xD;
&#xD;
          -  Willing to allow blood and tissue samples to be stored for future use to study HIV&#xD;
             infection, immune function, liver disease and additional mechanisms involved in liver&#xD;
             fibrosis among patients with HIV and/or HCV, which may not be related directly to the&#xD;
             specific objectives of this study protocol&#xD;
&#xD;
          -  Have a primary care physician&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Cause of liver fibrosis other than HCV or long-term antiretroviral therapy (ART)&#xD;
             treatment for HIV&#xD;
&#xD;
          -  Currently being treated for HCV&#xD;
&#xD;
          -  Evidence of active Hepatitis A, B or D infections&#xD;
&#xD;
          -  History or evidence of hepatocellular carcinoma&#xD;
&#xD;
          -  Unwillingness to undergo a liver biopsy pre-treatment and post-treatment, or to&#xD;
             undergo all other protocol required tests/procedures or return to the site for&#xD;
             required visits&#xD;
&#xD;
          -  Presence of contraindications to magnetic resonance imaging (e.g., presence of any&#xD;
             metal in the body, cardiac or neural pacemaker, aneurysm clip, cochlear implant,&#xD;
             claustrophobia)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gilead Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NIH Department of Laboratory Medicine</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Meissner EG, McLaughlin M, Matthews LA, Kanwar B, Bornstein JD, Kovacs JA, et al. Longitudinal hepatic and PBMC gene expression profiling of HIV and/or HCV-infected patients with advanced liver disease treated with simtuzumab, an anti-LOXL2 antibody [Abstract 448]. Hepatology AASLD Abstracts 2014;60 Number 4 (Suppl):421A.</citation>
  </reference>
  <reference>
    <citation>Han MAT, Gharib AM, Zhao X, Sinkus R, Rizvi BS, Matthews L, et al. Noninvasive Measures of Severity in Chronic Liver Disease, Moving Beyond Fibrosis [Abstract Sa1006]. Digestive Disease Week; 2015 16-19 May; Washington, D.C.</citation>
  </reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>October 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2012</study_first_posted>
  <results_first_submitted>September 19, 2019</results_first_submitted>
  <results_first_submitted_qc>September 19, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 9, 2019</results_first_posted>
  <disposition_first_submitted>November 17, 2015</disposition_first_submitted>
  <disposition_first_submitted_qc>November 17, 2015</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">December 16, 2015</disposition_first_posted>
  <last_update_submitted>October 22, 2019</last_update_submitted>
  <last_update_submitted_qc>October 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Liver Fibrosis</keyword>
  <keyword>Fibrosis</keyword>
  <keyword>HIV</keyword>
  <keyword>HCV</keyword>
  <keyword>GS-6624</keyword>
  <keyword>Hepatitis</keyword>
  <keyword>Hepatitis C</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Coinfection</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at 1 study site in the United States. The first participant was screened on 04 October 2012. The last study visit occurred on 17 October 2014.</recruitment_details>
      <pre_assignment_details>37 participants were screened.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Simtuzumab in HIV Participants</title>
          <description>Participants with human immunodeficiency virus (HIV) received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
        </group>
        <group group_id="P2">
          <title>Simtuzumab in HCV Participants</title>
          <description>Participants with hepatitis C virus (HCV) received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks.</description>
        </group>
        <group group_id="P3">
          <title>Simtuzumab in HIV/HCV Co-Infected Participants</title>
          <description>Participants co-infected with HIV and HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</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="6"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Safety Analysis Set included participants who received at least one dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Simtuzumab in HIV Participants</title>
          <description>Participants with HIV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
        </group>
        <group group_id="B2">
          <title>Simtuzumab in HCV Participants</title>
          <description>Participants with HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Simtuzumab in HIV/HCV Co-Infected Participants</title>
          <description>Participants co-infected with HIV and HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</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="4"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="8"/>
            <count group_id="B4" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56" spread="6.3"/>
                    <measurement group_id="B2" value="58" spread="5.0"/>
                    <measurement group_id="B3" value="54" spread="5.6"/>
                    <measurement group_id="B4" value="56" spread="5.6"/>
                  </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="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="14"/>
                  </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="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="15"/>
                  </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>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <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="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ishak Fibrosis Score</title>
          <description>The Ishak fibrosis score measures the degree of liver fibrosis (scarring) and ranges from 0 (best) to 6 (worst).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Stage 0</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>Stage 1</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>Stage 2</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>Stage 3</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stage 4</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stage 5</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stage 6</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hepatic Venous Pressure Gradient (HVPG)</title>
          <units>millimeters of Mercury (mm Hg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8" spread="5.3"/>
                    <measurement group_id="B2" value="9" spread="3.7"/>
                    <measurement group_id="B3" value="8" spread="3.7"/>
                    <measurement group_id="B4" value="8" spread="3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Morphometric Quantitative Collagen (MQC)</title>
          <units>percentage of MQC</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.24" spread="2.414"/>
                    <measurement group_id="B2" value="11.79" spread="9.582"/>
                    <measurement group_id="B3" value="12.75" spread="14.596"/>
                    <measurement group_id="B4" value="10.54" spread="11.312"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Alpha Smooth Muscle Actin (alpha SMA)</title>
          <units>percentage of alpha-SMA</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.59" spread="4.351"/>
                    <measurement group_id="B2" value="12.58" spread="12.184"/>
                    <measurement group_id="B3" value="13.32" spread="15.803"/>
                    <measurement group_id="B4" value="11.58" spread="12.549"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Magnetic Resonance Elastography (MRE)</title>
          <description>Liver fibrosis is measured by MRE in kilopascal (kPa)</description>
          <units>kPa</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.19" spread="0.370"/>
                    <measurement group_id="B2" value="2.01" spread="0.322"/>
                    <measurement group_id="B3" value="2.32" spread="0.487"/>
                    <measurement group_id="B4" value="2.20" spread="0.399"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Experiencing Treatment-Emergent Adverse Events</title>
        <time_frame>First dose date up to Week 24 plus 30 days</time_frame>
        <population>The Safety Analysis Set included participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Simtuzumab in HIV Participants</title>
            <description>Participants with HIV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
          </group>
          <group group_id="O2">
            <title>Simtuzumab in HCV Participants</title>
            <description>Participants with HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Simtuzumab in HIV/HCV Co-Infected Participants</title>
            <description>Participants co-infected with HIV and HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Experiencing Treatment-Emergent Adverse Events</title>
          <population>The Safety Analysis Set included participants who received at least one dose of study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                    <measurement group_id="O2" value="100"/>
                    <measurement group_id="O3" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24</title>
        <description>The Ishak fibrosis score measures the degree of liver fibrosis (scarring) and ranges from 0 (best) to 6 (worst). A negative value in change from baseline indicates an improvement and a positive value indicates worsening.</description>
        <time_frame>Baseline; Week 24</time_frame>
        <population>Participants in the Full Analysis Set (who were enrolled into the study and received at least 1 dose of study drug) with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Simtuzumab in HIV Participants</title>
            <description>Participants with HIV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
          </group>
          <group group_id="O2">
            <title>Simtuzumab in HCV Participants</title>
            <description>Participants with HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Simtuzumab in HIV/HCV Co-Infected Participants</title>
            <description>Participants co-infected with HIV and HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24</title>
          <description>The Ishak fibrosis score measures the degree of liver fibrosis (scarring) and ranges from 0 (best) to 6 (worst). A negative value in change from baseline indicates an improvement and a positive value indicates worsening.</description>
          <population>Participants in the Full Analysis Set (who were enrolled into the study and received at least 1 dose of study drug) with available data were analyzed.</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="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Fibrosis improved: -2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Fibrosis improved: -1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Fibrosis did not change: 0</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Fibrosis worsened: 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Fibrosis worsened: 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in HVPG at Week 24</title>
        <time_frame>Baseline; Week 24</time_frame>
        <population>Participants in the Full Analysis Set were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Simtuzumab in HIV Participants</title>
            <description>Participants with HIV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
          </group>
          <group group_id="O2">
            <title>Simtuzumab in HCV Participants</title>
            <description>Participants with HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Simtuzumab in HIV/HCV Co-Infected Participants</title>
            <description>Participants co-infected with HIV and HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in HVPG at Week 24</title>
          <population>Participants in the Full Analysis Set were analyzed.</population>
          <units>mm Hg</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="6"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" spread="2.4"/>
                    <measurement group_id="O2" value="0" spread="3.4"/>
                    <measurement group_id="O3" value="0" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in MQC at Week 24</title>
        <time_frame>Baseline; Week 24</time_frame>
        <population>Participants in the Full Analysis Set with liver biopsy area ≥ 4 mm^2 (adequate for morphometry measurements) were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Simtuzumab in HIV Participants</title>
            <description>Participants with HIV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
          </group>
          <group group_id="O2">
            <title>Simtuzumab in HCV Participants</title>
            <description>Participants with HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Simtuzumab in HIV/HCV Co-Infected Participants</title>
            <description>Participants co-infected with HIV and HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in MQC at Week 24</title>
          <population>Participants in the Full Analysis Set with liver biopsy area ≥ 4 mm^2 (adequate for morphometry measurements) were analyzed.</population>
          <units>percentage of MQC</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.07" spread="5.333"/>
                    <measurement group_id="O2" value="-2.54" spread="11.510"/>
                    <measurement group_id="O3" value="1.27" spread="9.612"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Alpha SMA at Week 24</title>
        <time_frame>Baseline; Week 24</time_frame>
        <population>Participants in the Full Analysis Set with liver biopsy area ≥ 4 mm^2 (adequate for morphometry measurements) were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Simtuzumab in HIV Participants</title>
            <description>Participants with HIV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
          </group>
          <group group_id="O2">
            <title>Simtuzumab in HCV Participants</title>
            <description>Participants with HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Simtuzumab in HIV/HCV Co-Infected Participants</title>
            <description>Participants co-infected with HIV and HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Alpha SMA at Week 24</title>
          <population>Participants in the Full Analysis Set with liver biopsy area ≥ 4 mm^2 (adequate for morphometry measurements) were analyzed.</population>
          <units>percentage of alpha-SMA</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.69" spread="3.938"/>
                    <measurement group_id="O2" value="5.27" spread="6.973"/>
                    <measurement group_id="O3" value="4.50" spread="7.669"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24</title>
        <time_frame>Baseline; Week 24</time_frame>
        <population>Participants in the Full Analysis Set with available data were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Simtuzumab in HIV Participants</title>
            <description>Participants with HIV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
          </group>
          <group group_id="O2">
            <title>Simtuzumab in HCV Participants</title>
            <description>Participants with HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Simtuzumab in HIV/HCV Co-Infected Participants</title>
            <description>Participants co-infected with HIV and HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24</title>
          <population>Participants in the Full Analysis Set with available data were analyzed.</population>
          <units>kPa</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="3"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.17" spread="0.141"/>
                    <measurement group_id="O2" value="0.09" spread="0.203"/>
                    <measurement group_id="O3" value="0.09" spread="0.085"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>First dose date to Week 24 plus 30 Days</time_frame>
      <desc>The Safety Analysis Set included participants who received at least one dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Simtuzumab in HIV Participants</title>
          <description>Participants with HIV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
        </group>
        <group group_id="E2">
          <title>Simtuzumab in HCV Participants</title>
          <description>Participants with HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks.</description>
        </group>
        <group group_id="E3">
          <title>Simtuzumab in HIV/HCV Co-Infected Participants</title>
          <description>Participants co-infected with HIV and HCV received simtuzumab 700 mg intravenously every 2 weeks over a period of 24 weeks while continuing on standard therapy for HIV.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.1</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="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Gallbladder injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.1</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="4" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphocytosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal tenderness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Aphthous stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Glossitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Infusion site rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Bilirubin conjugated increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Blood albumin decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase abnormal</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Blood creatinine decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>White blood cells urine positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Lower extremity mass</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cognitive disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Bipolar disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Glycosuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Ecchymosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Rash erythematous</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </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>After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:&#xD;
The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or&#xD;
The study has been completed at all study sites for at least 2 years</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Gilead Clinical Study Information Center</name_or_title>
      <organization>Gilead Sciences</organization>
      <phone>1-833-445-3230 (GILEAD-0)</phone>
      <email>GileadClinicalTrials@gilead.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/NCT01707472
org study id: GS-US-321-0107
nct id: NCT01707472
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of this study is to assess the safety and tolerability of simtuzumab
      (formerly GS-6624) in HIV and/or hepatitis C virus (HCV)-infected adults with evidence of
      liver fibrosis.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
time frame: First dose date up to Week 24 plus 30 days
measure: Number of Participants With a Change From Baseline in Ishak Fibrosis Stage Score at Week 24
time frame: Baseline; Week 24
description: The Ishak fibrosis score measures the degree of liver fibrosis (scarring) and ranges from 0 (best) to 6 (worst). A negative value in change from baseline indicates an improvement and a positive value indicates worsening.
measure: Change From Baseline in HVPG at Week 24
time frame: Baseline; Week 24
measure: Change From Baseline in MQC at Week 24
time frame: Baseline; Week 24
measure: Change From Baseline in Alpha SMA at Week 24
time frame: Baseline; Week 24
measure: Change From Baseline in Liver Fibrosis as Estimated by MRE at Week 24
time frame: Baseline; Week 24
arm group label: Simtuzumab in HIV Patients
arm group type: Experimental
description: HIV-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV.
arm group label: Simtuzumab in HCV Patients
arm group type: Experimental
description: HCV-infected participants will receive simtuzumab every 2 weeks for 24 weeks.
arm group label: Simtuzumab in HIV/HCV Co-Infected Patients
arm group type: Experimental
description: HIV/HCV co-infected participants will receive simtuzumab every 2 weeks for 24 weeks while continuing on standard therapy for HIV.
intervention type: Biological
intervention name: Simtuzumab
description: 700 mg intravenously for a total of 12 infusions.
arm group label: Simtuzumab in HCV Patients
arm group label: Simtuzumab in HIV Patients
arm group label: Simtuzumab in HIV/HCV Co-Infected Patients
other name: Anti-LOXL2 Monoclonal Antibody
other name: GS-6624
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gilead Study Director
role: Study Director
affiliation: Gilead Sciences
facility: 
country: United States
citation: Meissner EG, McLaughlin M, Matthews LA, Kanwar B, Bornstein JD, Kovacs JA, et al. Longitudinal hepatic and PBMC gene expression profiling of HIV and/or HCV-infected patients with advanced liver disease treated with simtuzumab, an anti-LOXL2 antibody [Abstract 448]. Hepatology AASLD Abstracts 2014;60 Number 4 (Suppl):421A.
citation: Han MAT, Gharib AM, Zhao X, Sinkus R, Rizvi BS, Matthews L, et al. Noninvasive Measures of Severity in Chronic Liver Disease, Moving Beyond Fibrosis [Abstract Sa1006]. Digestive Disease Week; 2015 16-19 May; Washington, D.C.
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Coinfection
mesh term: Hepatitis
mesh term: Liver Cirrhosis
mesh term: Fibrosis
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 