<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/NCT01672853</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-321-0102</org_study_id>
    <secondary_id>2012-002473-61</secondary_id>
    <nct_id>NCT01672853</nct_id>
  </id_info>
  <brief_title>Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults With Primary Sclerosing Cholangitis (PSC)</brief_title>
  <official_title>A Phase 2b, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and Efficacy of GS-6624, a Monoclonal Antibody Against Lysyl Oxidase Like 2 (LOXL2) in Subjects With Primary Sclerosing Cholangitis (PSC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </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 purpose of this study is to evaluate whether simtuzumab (GS-6624) is effective at&#xD;
      preventing the progression of liver fibrosis in adults with primary sclerosing cholangitis&#xD;
      (PSC).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 4, 2013</start_date>
  <completion_date type="Actual">August 24, 2016</completion_date>
  <primary_completion_date type="Actual">August 8, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in MQC on Liver Biopsy at Week 96</measure>
    <time_frame>Baseline; Week 96</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event</measure>
    <time_frame>First dose date up to Week 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Study Drug Exposure</measure>
    <time_frame>First dose date up to Week 96</time_frame>
    <description>The average SIM exposure was summarized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality</measure>
    <time_frame>First dose date up to Week 96 plus 30 days</time_frame>
    <description>A treatment-emergent graded laboratory abnormality was defined as an increase of at least 1 abnormality grade from the predose assessment and occurring after the predose visit and on or before the date of the administration of study drug plus 30 days. The most severe graded abnormality from all tests was counted for each participant [Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (life-threatening)].</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">235</enrollment>
  <condition>Primary Sclerosing Cholangitis (PSC)</condition>
  <arm_group>
    <arm_group_label>Treatment Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Simtuzumab 75 mg for 96 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Simtuzumab 125 mg for 96 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Arm C</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo for 96 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Simtuzumab</intervention_name>
    <description>Subcutaneous injections weekly for a total of 96 injections</description>
    <arm_group_label>Treatment Arm A</arm_group_label>
    <arm_group_label>Treatment Arm B</arm_group_label>
    <other_name>GS-6624</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subcutaneous injections weekly for a total of 96 injections</description>
    <arm_group_label>Treatment Arm C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Adult Individuals (aged 18-70) with chronic cholestatic liver disease of at least 6&#xD;
             months.&#xD;
&#xD;
          -  Liver biopsy consistent with PSC: If a liver biopsy has been performed within 3 months&#xD;
             of the screening visit, tissue from that biopsy may be used as the screening biopsy.&#xD;
             Slides would be re-cut from the existing tissue block and submitted for central reader&#xD;
             assessment. Some individuals with PSC may have a normal liver biopsy, in the event of&#xD;
             a normal liver biopsy, the individual must have an abnormal magnetic resonance&#xD;
             cholangiopancreatography (MRCP).&#xD;
&#xD;
          -  MRCP consistent with PSC: Some individuals with PSC may have a normal MRCP; in the&#xD;
             event of a normal MRCP, the individual must have an abnormal liver biopsy.&#xD;
&#xD;
          -  Exclusion of other causes of liver disease including viral hepatitis ,alcoholic liver&#xD;
             disease,primary biliary cirrhosis and secondary sclerosing cholangitis&#xD;
&#xD;
          -  Must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 x&#xD;
             the Central Laboratory Upper Limit of Normal (clULN)&#xD;
&#xD;
          -  Must have serum creatinine &lt; 2.0 mg/dL&#xD;
&#xD;
          -  A negative serum pregnancy test is required for female individuals of childbearing&#xD;
             potential&#xD;
&#xD;
          -  All sexually active female individuals of childbearing potential must agree to use a&#xD;
             protocol recommended method of contraception during heterosexual intercourse&#xD;
             throughout the study and for 90 days following the last dose of study medication&#xD;
&#xD;
          -  Lactating females must agree to discontinue nursing before starting study treatment&#xD;
&#xD;
          -  Males if not vasectomized, are required to use barrier contraception (condom plus&#xD;
             spermicide) during intercourse from the screening through the study completion and for&#xD;
             90 days following the last dose of study drug&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breast feeding&#xD;
&#xD;
          -  Evidence of hepatic decompensation present, including ascites, episodes of hepatic&#xD;
             encephalopathy, variceal bleeding or a prolonged prothrombin time/international&#xD;
             normalized ratio (PT/INR)&#xD;
&#xD;
          -  Positive for hepatitis C virus (HCV) RNA&#xD;
&#xD;
          -  Positive for HBsAg&#xD;
&#xD;
          -  Positive for anti-mitochondrial antibody&#xD;
&#xD;
          -  Alcohol consumption greater than 21oz/week for males or 14oz/week for females&#xD;
&#xD;
          -  Moderately active ulcerative colitis (UC) defined as either a partial Mayo score of &gt;&#xD;
             4, bleeding score of &gt;1, or current use of oral corticosteroid therapy and/or any&#xD;
             inhibitor of Tumor necrosis factor-α (TNF-α) or α4β7 integrin antagonist&#xD;
&#xD;
          -  Positive urine screen for amphetamines, cocaine or opiates (i.e. heroin, morphine) at&#xD;
             screening. Individuals on stable methadone or buprenorphine maintenance treatment for&#xD;
             at least 6 months prior to screening may be included in the study. Individuals with a&#xD;
             positive urine drug screen due to prescription opioid-based medication are eligible if&#xD;
             the prescription and diagnosis are reviewed and approved by the investigator&#xD;
&#xD;
          -  Clinically significant cardiac disease&#xD;
&#xD;
          -  History of cholangiocarcinoma&#xD;
&#xD;
          -  History of other cancers,other than non-melanomatous skin cancer, within 5 years prior&#xD;
             to screening&#xD;
&#xD;
          -  Ascending cholangitis within 60 days of screening&#xD;
&#xD;
          -  Presence of a percutaneous drain or bile duct stent&#xD;
&#xD;
          -  Known hypersensitivity to the investigation product or any of its formulation&#xD;
             excipients&#xD;
&#xD;
          -  History of bleeding diathesis within 6 months of screening&#xD;
&#xD;
          -  Unavailable for follow-up assessment or concern for individual's compliance with the&#xD;
             protocol procedures;&#xD;
&#xD;
          -  Participation in an investigational trial of a drug or device within 30 days prior to&#xD;
             screening&#xD;
&#xD;
          -  Major surgical procedure within 30 days prior to screening or the presence of an open&#xD;
             wound&#xD;
&#xD;
        Note: Other protocol defined Inclusion/Exclusion criteria may apply.&#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>Gilead Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Arizona Health Sciences Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern California Liver Center</name>
      <address>
        <city>Chula Vista</city>
        <state>California</state>
        <zip>91910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern California Liver Centers</name>
      <address>
        <city>Coronado</city>
        <state>California</state>
        <zip>92118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scripps Clinic</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Verterans Adminstration Hospital</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Davis Medical Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of San Diego Medical Center</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami 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>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indianapolis Gastroenterology Research Foundation</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iowa Digestive Disease Center</name>
      <address>
        <city>Clive</city>
        <state>Iowa</state>
        <zip>50325</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tulane University Health Sciences Center</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Walter Reed National Military Medical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20889</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>01125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Gastroenterology, PA</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Louis University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical College</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Clinical Research Institute</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Case Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Gastroenterology</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brooke Army Medical Center</name>
      <address>
        <city>Fort Sam Houston</city>
        <state>Texas</state>
        <zip>78234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke Episcopal Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alamo Medical Research</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Intermountain Medical Center</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia Health Center</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liver Institute of Virginia</name>
      <address>
        <city>Newport News</city>
        <state>Virginia</state>
        <zip>23603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Digestive and Liver Disease Specialists</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bon Secours Richmond Health System</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University Health System</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Mason Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Erasme</name>
      <address>
        <city>Brussels</city>
        <zip>1070</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Université Catholique de Louvain</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Antwerpen</name>
      <address>
        <city>Edegem</city>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent</name>
      <address>
        <city>Gent</city>
        <zip>B-9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Alberta</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Manitoba</name>
      <address>
        <city>Winnepeg</city>
        <state>Manitoba</state>
        <zip>R3E 3P4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dalhousie University</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 2Y9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Science Center</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6C 5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto Liver Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M6H 3M1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hvidovre Hospital</name>
      <address>
        <city>Hvidovre</city>
        <zip>DK-2650</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Kobenhavn O</city>
        <zip>DK-2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Århus Universitetshospital, Århus Sygehus</name>
      <address>
        <city>Århus C</city>
        <zip>DK-8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Johann Wolfgang Goethe Universitat</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gastroenterologisch Hepatologisches Zentrum Kiel</name>
      <address>
        <city>Kiel</city>
        <zip>24146</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>EUGASTRO GmbH</name>
      <address>
        <city>Leipzig</city>
        <zip>4103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera San Camillo Forlanini</name>
      <address>
        <city>Roma</city>
        <zip>144</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Città della Salute e della Scienza di Torino</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eramus MC</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015 CE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <state>Cataluna</state>
        <zip>8035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Puerta de Hierro</name>
      <address>
        <city>Majadahonda</city>
        <zip>28222</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Donostia</name>
      <address>
        <city>San Sebastian</city>
        <zip>20080</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avd för invärtesmedicin och klinisk nutrition</name>
      <address>
        <city>Goteborg</city>
        <zip>413 45</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Queen Elizabeth Hospital</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2WB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Radcliffe Hospital</name>
      <address>
        <city>Headington</city>
        <zip>OX3 9DU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial College Healthcare NHS Trust- St. Mary's Hospital</name>
      <address>
        <city>London</city>
        <zip>W2 1NY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London</name>
      <address>
        <city>London</city>
        <zip>WC1E 6HX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norfolk and Norwich University Hospital</name>
      <address>
        <city>Norwich</city>
        <zip>NR4 7UY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nottingham</name>
      <address>
        <city>Nottingham</city>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Denmark</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Shea P, Hirschfield G, Shiffman M, McColgan B, Goodman Z, Myers, R, et al. Common variation near glial-derived neurotrophic factor is associated with progression of hepatic collagen content in a genome-wide association study of liver fibrosis phenotypes in patients with primary sclerosing cholangitis. J Hepatol 2017; 66 (1): S4-S5.</citation>
  </results_reference>
  <results_reference>
    <citation>Muir A, Goodman Z, Levy C, Janssen H, Montano-Loza A, Bowlus C, et al. Efficacy and safety of simtuzumab for the treatment of primary sclerosing cholangitis: results of a phase 2b, dose-ranging, randomized, placebo-controlled trial. J Hepatol 2017; 66 (1): S73.</citation>
  </results_reference>
  <results_reference>
    <citation>Bowlus CL, Patel K, Hirschfield G, Guha I, Chapman R, Chazouilleres O, et al. Prospective validation of the Enhanced Liver Fibrosis test for the prediction of disease progression in a randomized trial of patients with primary sclerosing cholangitis. J Hepatol 2017; 66 (1): S359.</citation>
  </results_reference>
  <results_reference>
    <citation>Levy C, Eksteen B, Shiffman M, Janssen H, Montano-Loza A, Ding D, et al. Prospective validation of serum alkaline phosphatase for the prediction of disease progression in a randomized trial of patients with primary sclerosing cholangitis. J Hepatol 2017; 66 (1): S360-S361.</citation>
  </results_reference>
  <results_reference>
    <citation>Levy C, Shiffman M, Caldwell S, Luketic V, Invernizzi P, Minuk G, et al. Serum fibroblast growth factor 19, 7α-Hydroxy-4-Cholesten-3-one, and bile acids and their associations with clinical characteristics in primary sclerosing cholangitis. J Hepatol 2017; 66 (1): S361.</citation>
  </results_reference>
  <results_reference>
    <citation>French D, Huntzicker EG, Goodman ZD, Shea PR, Ding D, Aguilar Schall, RE, et al. Hepatic expression of lysyl oxidase-like-2 (LOXL2) in primary sclerosing cholangitis (PSC). Hepatol 2016; 64 (1): 194A.</citation>
  </results_reference>
  <results_reference>
    <citation>Bowlus CL, Montano-Loza AJ, Invernizzi P, Chazouilleres O, Hirschfield G, Metselaar HJ, et al. Liver stiffness measurement by transient elastography for the prediction of fibrosis in patients with primary sclerosing cholangitis in a randomized trial of simtuzumab. J Hepatol 2016; 64 (2): S434.</citation>
  </results_reference>
  <results_reference>
    <citation>Goodman Z, Patel K, Guha I, Hameed B, Kowdley K, Alaparthi L, et al. Correlations between hepatic morphometric collagen content, histologic fibrosis stage, and serum markers in patients with primary sclerosing cholangitis (PSC). J Hepatol 2016; 64 (2): S652-S653.</citation>
  </results_reference>
  <results_reference>
    <citation>Muir AJ, Goodman Z, Bowlus CL, Caldwell S, Invernizzi P, Luketic V, et al. Serum lysyl oxidase-like-2 (SLOXL2) levels correlate with disease severity in patients with primary sclerosing cholangitis. J Hepatol 2016; 64 (2): S428.</citation>
  </results_reference>
  <results_reference>
    <citation>Shea PR, Eksteen B, Hirschfield GM, Shiffman ML, Janssen HLA, Montano-Loza AJ, et al. Genome-wide association study (GWAS) of liver fibrosis phenotypes in patients with primary sclerosing cholangitis (PSC) reveals common genetic variation influencing serum levels of lysyl oxidase-like-2 (LOXL2). J Hepatol 2016; 64 (2): S180-S182.</citation>
  </results_reference>
  <results_reference>
    <citation>Manns MP, Eksteen B, Shiffman ML, Levy C, Kowdley KV, Montano-Loza AJ, et al. Association between elevated serum IgG4 (sIgG4) concentrations and the phenotype of patients with primary sclerosing cholangitis (PSC). Hepatol 2015; 62 (1): 515A.</citation>
  </results_reference>
  <results_reference>
    <citation>Bowlus CL, Patel K, Chuha IN, Chapman RW, Chazouilleres O, Chalasani NP, et al. Validation of serum fibrosis marker panels in patients with primary sclerosing cholangitis (PSC) in a randomized trial of simtuzumab. Hepatol 2015; 62 (1): 519A.</citation>
  </results_reference>
  <results_reference>
    <citation>French D, Goodman ZD, Huntzicker EG, Newstrom D, Karnik S, Smith V, et al. Expression of matrix metalloproteinase 9 (MMP9) and the apoptosis signal-regulating kinase 1 (ASK1) pathway activation marker, phospho-P38 (p-P38), in primary sclerosing cholangitis (PSC). Hepatol 2015; 62 (1): 523A-524A.</citation>
  </results_reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 22, 2012</study_first_submitted>
  <study_first_submitted_qc>August 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2012</study_first_posted>
  <results_first_submitted>October 3, 2019</results_first_submitted>
  <results_first_submitted_qc>October 3, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 22, 2019</results_first_posted>
  <disposition_first_submitted>February 23, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>February 23, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">February 24, 2017</disposition_first_posted>
  <last_update_submitted>October 3, 2019</last_update_submitted>
  <last_update_submitted_qc>October 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PSC</keyword>
  <keyword>Sclerosis</keyword>
  <keyword>Monoclonal antibody</keyword>
  <keyword>LOXL2</keyword>
  <keyword>Simtuzumab</keyword>
  <keyword>Primary sclerosing cholangitis</keyword>
  <keyword>Liver fibrosis</keyword>
  <keyword>Liver disease</keyword>
  <keyword>MRCP</keyword>
  <keyword>MRE</keyword>
  <keyword>Liver biopsy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholangitis</mesh_term>
    <mesh_term>Cholangitis, Sclerosing</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at study sites in North America and Europe. The first participant was screened on 4 March 2013. The last study visit occurred on 24 August 2016.</recruitment_details>
      <pre_assignment_details>298 participants were screened.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>SIM 75 mg</title>
          <description>Simtuzumab (SIM) 75 mg subcutaneous injections weekly for 96 weeks</description>
        </group>
        <group group_id="P2">
          <title>SIM 125 mg</title>
          <description>SIM 125 mg subcutaneous injections weekly for 96 weeks</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>Placebo subcutaneous injections weekly for 96 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="79"/>
                <participants group_id="P2" count="77"/>
                <participants group_id="P3" count="79"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="69"/>
                <participants group_id="P2" count="60"/>
                <participants group_id="P3" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="17"/>
                <participants group_id="P3" count="14"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Specified Criteria for Withdraw</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Investigator's Discretion</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrew Consent</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Randomized but Never Treated</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_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>SIM 75 mg</title>
          <description>SIM 75 mg subcutaneous injections weekly for 96 weeks</description>
        </group>
        <group group_id="B2">
          <title>SIM 125 mg</title>
          <description>SIM 125 mg subcutaneous injections weekly for 96 weeks</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>Placebo subcutaneous injections weekly for 96 weeks</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="79"/>
            <count group_id="B2" value="77"/>
            <count group_id="B3" value="78"/>
            <count group_id="B4" value="234"/>
          </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="45" spread="11.3"/>
                    <measurement group_id="B2" value="43" spread="10.1"/>
                    <measurement group_id="B3" value="44" spread="12.8"/>
                    <measurement group_id="B4" value="44" spread="11.5"/>
                  </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="27"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="33"/>
                    <measurement group_id="B4" value="85"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="52"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="45"/>
                    <measurement group_id="B4" value="149"/>
                  </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="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="78"/>
                    <measurement group_id="B2" value="73"/>
                    <measurement group_id="B3" value="77"/>
                    <measurement group_id="B4" value="228"/>
                  </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>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>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="71"/>
                    <measurement group_id="B2" value="68"/>
                    <measurement group_id="B3" value="62"/>
                    <measurement group_id="B4" value="201"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sweden</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Netherlands</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Belgium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="43"/>
                    <measurement group_id="B4" value="120"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Denmark</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>France</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="7"/>
                  </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="5.6" spread="5.09"/>
                    <measurement group_id="B2" value="5.6" spread="3.36"/>
                    <measurement group_id="B3" value="5.1" spread="3.98"/>
                    <measurement group_id="B4" value="5.4" spread="4.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in MQC on Liver Biopsy at Week 96</title>
        <time_frame>Baseline; Week 96</time_frame>
        <population>Participants in the Full Analysis Set (participants who were randomized 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>SIM 75 mg</title>
            <description>SIM 75 mg subcutaneous injections weekly for 96 weeks</description>
          </group>
          <group group_id="O2">
            <title>SIM 125 mg</title>
            <description>SIM 125 mg subcutaneous injections weekly for 96 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo subcutaneous injections weekly for 96 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in MQC on Liver Biopsy at Week 96</title>
          <population>Participants in the Full Analysis Set (participants who were randomized into the study and received at least 1 dose of study drug) with available data 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="61"/>
                <count group_id="O2" value="61"/>
                <count group_id="O3" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="5.78"/>
                    <measurement group_id="O2" value="0.5" spread="6.94"/>
                    <measurement group_id="O3" value="0.0" spread="4.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>A mixed-effect model for repeated measures (MMRM) with an unstructured variance-covariance matrix for each participant was used to calculate a point estimate and a 95% confidence interval (CI) for the treatment difference between each treatment arm and placebo in least squares mean (LSMean) change from baseline in MQC at Week 96. With MMRM setting, all participants with available data from the 3 treatment groups with change in MQC at Week 48 and/or Week 96 contributed to the overall model.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Difference in LS Mean</param_type>
            <param_value>-0.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.3</ci_lower_limit>
            <ci_upper_limit>1.6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>A MMRM with an unstructured variancecovariance matrix for each participant was used to calculate a point estimate and a 95% CI for the treatment difference between each treatment arm and placebo in LSMean change from baseline in MQC at Week 96. With MMRM setting, all participants with available data from the 3 treatment groups with change in MQC at Week 48 and/or Week 96 contributed to the overall model.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Difference in LS Mean</param_type>
            <param_value>1.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.0</ci_lower_limit>
            <ci_upper_limit>3.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event</title>
        <time_frame>First dose date up to Week 96</time_frame>
        <population>The Safety Analysis Set included participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>SIM 75 mg</title>
            <description>SIM 75 mg subcutaneous injections weekly for 96 weeks</description>
          </group>
          <group group_id="O2">
            <title>SIM 125 mg</title>
            <description>SIM 125 mg subcutaneous injections weekly for 96 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo subcutaneous injections weekly for 96 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event</title>
          <population>The Safety Analysis Set included participants who received at least 1 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="79"/>
                <count group_id="O2" value="77"/>
                <count group_id="O3" value="78"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1"/>
                    <measurement group_id="O2" value="7.8"/>
                    <measurement group_id="O3" value="10.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Study Drug Exposure</title>
        <description>The average SIM exposure was summarized.</description>
        <time_frame>First dose date up to Week 96</time_frame>
        <population>Participants in the Safety Analysis Set were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>SIM 75 mg</title>
            <description>SIM 75 mg subcutaneous injections weekly for 96 weeks</description>
          </group>
          <group group_id="O2">
            <title>SIM 125 mg</title>
            <description>SIM 125 mg subcutaneous injections weekly for 96 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo subcutaneous injections weekly for 96 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Study Drug Exposure</title>
          <description>The average SIM exposure was summarized.</description>
          <population>Participants in the Safety Analysis Set were analyzed.</population>
          <units>weeks</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="79"/>
                <count group_id="O2" value="77"/>
                <count group_id="O3" value="78"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.0" spread="15.33"/>
                    <measurement group_id="O2" value="83.8" spread="26.12"/>
                    <measurement group_id="O3" value="87.4" spread="22.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality</title>
        <description>A treatment-emergent graded laboratory abnormality was defined as an increase of at least 1 abnormality grade from the predose assessment and occurring after the predose visit and on or before the date of the administration of study drug plus 30 days. The most severe graded abnormality from all tests was counted for each participant [Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (life-threatening)].</description>
        <time_frame>First dose date up to Week 96 plus 30 days</time_frame>
        <population>Participants in the Safety Analysis Set with at least one post-baseline measurement were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>SIM 75 mg</title>
            <description>SIM 75 mg subcutaneous injections weekly for 96 weeks</description>
          </group>
          <group group_id="O2">
            <title>SIM 125 mg</title>
            <description>SIM 125 mg subcutaneous injections weekly for 96 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo subcutaneous injections weekly for 96 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality</title>
          <description>A treatment-emergent graded laboratory abnormality was defined as an increase of at least 1 abnormality grade from the predose assessment and occurring after the predose visit and on or before the date of the administration of study drug plus 30 days. The most severe graded abnormality from all tests was counted for each participant [Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (life-threatening)].</description>
          <population>Participants in the Safety Analysis Set with at least one post-baseline measurement were analyzed.</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="79"/>
                <count group_id="O2" value="77"/>
                <count group_id="O3" value="78"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.4"/>
                    <measurement group_id="O2" value="16.9"/>
                    <measurement group_id="O3" value="17.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.6"/>
                    <measurement group_id="O2" value="20.8"/>
                    <measurement group_id="O3" value="25.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.1"/>
                    <measurement group_id="O2" value="46.8"/>
                    <measurement group_id="O3" value="48.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.4"/>
                    <measurement group_id="O2" value="13.0"/>
                    <measurement group_id="O3" value="7.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>First dose date up to Week 96 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>SIM 75 mg</title>
          <description>SIM 75 mg subcutaneous injections weekly for 96 weeks</description>
        </group>
        <group group_id="E2">
          <title>SIM 125 mg</title>
          <description>SIM 125 mg subcutaneous injections weekly for 96 weeks</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>Placebo subcutaneous injections weekly for 96 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.1</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="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Colitis ulcerative</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Diverticular perforation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Haematemesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Oesophageal varices haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pancreatitis acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </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="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Systemic inflammatory response syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Bile duct stone</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Cholangitis acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gallbladder perforation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Jaundice cholestatic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Portal vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cholangitis infective</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gastrointestinal infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Infected skin ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pelvic abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Peritonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Streptococcal bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Intestinal anastomosis complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Post procedural complication</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Postoperative fever</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Procedural complication</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Stoma obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Liver function test increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Failure to thrive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Benign biliary neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Cholangiocarcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Hepatocellular carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Lipoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rectal adenoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Post-traumatic stress disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Calculus urinary</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Renal colic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Drug eruption</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombophlebitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 19.1</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="71" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="72" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="75" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="18" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Colitis ulcerative</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Varices oesophageal</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="16" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Jaundice</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </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="4" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="78"/>
              </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="5" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </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="14" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="31" subjects_at_risk="78"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="78"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="79"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="77"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="78"/>
              </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/NCT01672853
org study id: GS-US-321-0102
secondary id: 2012-002473-61
nct id: NCT01672853
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate whether simtuzumab (GS-6624) is effective at
      preventing the progression of liver fibrosis in adults with primary sclerosing cholangitis
      (PSC).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change From Baseline in MQC on Liver Biopsy at Week 96
time frame: Baseline; Week 96
measure: Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
time frame: First dose date up to Week 96
measure: Study Drug Exposure
time frame: First dose date up to Week 96
description: The average SIM exposure was summarized.
measure: Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality
time frame: First dose date up to Week 96 plus 30 days
description: A treatment-emergent graded laboratory abnormality was defined as an increase of at least 1 abnormality grade from the predose assessment and occurring after the predose visit and on or before the date of the administration of study drug plus 30 days. The most severe graded abnormality from all tests was counted for each participant [Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (life-threatening)].
arm group label: Treatment Arm A
arm group type: Experimental
description: Simtuzumab 75 mg for 96 weeks
arm group label: Treatment Arm B
arm group type: Experimental
description: Simtuzumab 125 mg for 96 weeks
arm group label: Treatment Arm C
arm group type: Placebo Comparator
description: Placebo for 96 weeks
intervention type: Biological
intervention name: Simtuzumab
description: Subcutaneous injections weekly for a total of 96 injections
arm group label: Treatment Arm A
arm group label: Treatment Arm B
other name: GS-6624
intervention type: Biological
intervention name: Placebo
description: Subcutaneous injections weekly for a total of 96 injections
arm group label: Treatment Arm C
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Gilead Study Director
role: Study Director
affiliation: Gilead Sciences
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country: Belgium
country: Canada
country: Denmark
country: Germany
country: Italy
country: Netherlands
country: Spain
country: Sweden
country: United Kingdom
country: United States
citation: Shea P, Hirschfield G, Shiffman M, McColgan B, Goodman Z, Myers, R, et al. Common variation near glial-derived neurotrophic factor is associated with progression of hepatic collagen content in a genome-wide association study of liver fibrosis phenotypes in patients with primary sclerosing cholangitis. J Hepatol 2017; 66 (1): S4-S5.
citation: Muir A, Goodman Z, Levy C, Janssen H, Montano-Loza A, Bowlus C, et al. Efficacy and safety of simtuzumab for the treatment of primary sclerosing cholangitis: results of a phase 2b, dose-ranging, randomized, placebo-controlled trial. J Hepatol 2017; 66 (1): S73.
citation: Bowlus CL, Patel K, Hirschfield G, Guha I, Chapman R, Chazouilleres O, et al. Prospective validation of the Enhanced Liver Fibrosis test for the prediction of disease progression in a randomized trial of patients with primary sclerosing cholangitis. J Hepatol 2017; 66 (1): S359.
citation: Levy C, Eksteen B, Shiffman M, Janssen H, Montano-Loza A, Ding D, et al. Prospective validation of serum alkaline phosphatase for the prediction of disease progression in a randomized trial of patients with primary sclerosing cholangitis. J Hepatol 2017; 66 (1): S360-S361.
citation: Levy C, Shiffman M, Caldwell S, Luketic V, Invernizzi P, Minuk G, et al. Serum fibroblast growth factor 19, 7α-Hydroxy-4-Cholesten-3-one, and bile acids and their associations with clinical characteristics in primary sclerosing cholangitis. J Hepatol 2017; 66 (1): S361.
citation: French D, Huntzicker EG, Goodman ZD, Shea PR, Ding D, Aguilar Schall, RE, et al. Hepatic expression of lysyl oxidase-like-2 (LOXL2) in primary sclerosing cholangitis (PSC). Hepatol 2016; 64 (1): 194A.
citation: Bowlus CL, Montano-Loza AJ, Invernizzi P, Chazouilleres O, Hirschfield G, Metselaar HJ, et al. Liver stiffness measurement by transient elastography for the prediction of fibrosis in patients with primary sclerosing cholangitis in a randomized trial of simtuzumab. J Hepatol 2016; 64 (2): S434.
citation: Goodman Z, Patel K, Guha I, Hameed B, Kowdley K, Alaparthi L, et al. Correlations between hepatic morphometric collagen content, histologic fibrosis stage, and serum markers in patients with primary sclerosing cholangitis (PSC). J Hepatol 2016; 64 (2): S652-S653.
citation: Muir AJ, Goodman Z, Bowlus CL, Caldwell S, Invernizzi P, Luketic V, et al. Serum lysyl oxidase-like-2 (SLOXL2) levels correlate with disease severity in patients with primary sclerosing cholangitis. J Hepatol 2016; 64 (2): S428.
citation: Shea PR, Eksteen B, Hirschfield GM, Shiffman ML, Janssen HLA, Montano-Loza AJ, et al. Genome-wide association study (GWAS) of liver fibrosis phenotypes in patients with primary sclerosing cholangitis (PSC) reveals common genetic variation influencing serum levels of lysyl oxidase-like-2 (LOXL2). J Hepatol 2016; 64 (2): S180-S182.
citation: Manns MP, Eksteen B, Shiffman ML, Levy C, Kowdley KV, Montano-Loza AJ, et al. Association between elevated serum IgG4 (sIgG4) concentrations and the phenotype of patients with primary sclerosing cholangitis (PSC). Hepatol 2015; 62 (1): 515A.
citation: Bowlus CL, Patel K, Chuha IN, Chapman RW, Chazouilleres O, Chalasani NP, et al. Validation of serum fibrosis marker panels in patients with primary sclerosing cholangitis (PSC) in a randomized trial of simtuzumab. Hepatol 2015; 62 (1): 519A.
citation: French D, Goodman ZD, Huntzicker EG, Newstrom D, Karnik S, Smith V, et al. Expression of matrix metalloproteinase 9 (MMP9) and the apoptosis signal-regulating kinase 1 (ASK1) pathway activation marker, phospho-P38 (p-P38), in primary sclerosing cholangitis (PSC). Hepatol 2015; 62 (1): 523A-524A.
responsible party type: Sponsor
mesh term: Cholangitis
mesh term: Cholangitis, Sclerosing
participant flow: 
baseline: 
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reported events: 
certain agreements: 
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