<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/NCT02250807</url>
  </required_header>
  <id_info>
    <org_study_id>CR105429</org_study_id>
    <secondary_id>TMC435HPC3021</secondary_id>
    <secondary_id>2014-003446-27</secondary_id>
    <nct_id>NCT02250807</nct_id>
    <nct_alias>NCT02256176</nct_alias>
  </id_info>
  <brief_title>Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Subjects With Chronic Genotype 4 Hepatitis C Virus Infection</brief_title>
  <official_title>A Phase 3, Multicenter, Open-Label, Single-Arm Study to Investigate the Efficacy and Safety of a 12-Week Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naive or -Experienced Subjects With Chronic Genotype 4 Hepatitis C Virus Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen R&amp;D Ireland</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen R&amp;D Ireland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to show superiority of simeprevir (SMV) in combination with&#xD;
      sofosbuvir for 12 weeks versus a historical control. Historical control will be a composite&#xD;
      of the observed historical sustained virological response at Week 12 (SVR12) rates of SMV in&#xD;
      combination with (pegylated) interferon (PegIFN)/ribavirin (RBV) of the subpopulations in&#xD;
      study HPC3011 (NCT01567735) and will depend on the percentage of treatment-naive, prior&#xD;
      relapser, prior non-responder, interferon (IFN)-intolerant and other subjects enrolled in&#xD;
      this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 3, open-label (all people know the identity of the intervention), single-arm,&#xD;
      multicenter study (conducted at multiple sites). The study consists of 3 periods: a Screening&#xD;
      period (up to 4 weeks), Treatment period (12 Weeks) and Post treatment follow-up period&#xD;
      (until 24 weeks after end of treatment). The duration of the subjects' participation will be&#xD;
      approximately 40 weeks. In the treatment period subjects will receive oral capsule simeprevir&#xD;
      along with oral tablet sofosbuvir once daily for 12 weeks. Primarily efficacy will be&#xD;
      evaluated as percentage of subjects with sustained virologic response at Week 12 after the&#xD;
      end of treatment. Subjects' safety will be monitored throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)</measure>
    <time_frame>12 weeks after EOT</time_frame>
    <description>SVR12 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (&lt;) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 12 weeks after actual EOT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Therapy (SVR4)</measure>
    <time_frame>4 weeks after EOT</time_frame>
    <description>SVR4 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (&lt;) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 4 weeks after actual EOT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Therapy (SVR24)</measure>
    <time_frame>At 24 weeks after EOT</time_frame>
    <description>Participants were considered to have reached SVR24, if at the time point of SVR24 (that is [i.e.], 24 weeks after the end of treatment [EOT]) the following condition has been met: HCV RNA &lt; lower limit of quantification (LLOQ), i.e., 15 IU/mL, detectable or undetectable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)</measure>
    <time_frame>Week 2, 3, 4, 12 and EOT</time_frame>
    <description>Percentage of participants with HCV RNA less than (&lt;) 15 IU/mL undetectable or detectable or detectable /undetectable at specific time points were observed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With On-Treatment Failure</measure>
    <time_frame>through 12 weeks (EOT)</time_frame>
    <description>Participants were considered on-treatment failures if they have at EOT (confirmed) detectable HCV RNA, i.e., &lt;LLOQ detectable or &gt;=LLOQ.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Viral Breakthrough</measure>
    <time_frame>Up to follow-up Week 24</time_frame>
    <description>Participants with confirmed &gt;1.0 log10 increase in HCV RNA from nadir or confirmed HCV RNA &gt;100 IU/mL in participants who had previously achieved HCV RNA &lt;LLOQ.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Viral Relapse</measure>
    <time_frame>Up to follow-up week 24</time_frame>
    <description>Participants were considered to have viral relapse if they did not achieve SVR12 and meet the following conditions: 1) at EOT, HCV RNA less than (&lt;)LLOQ, undetectable, and 2) during the follow-up period, HCV RNA greater than or equal to (&gt;=)LLOQ.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Chronic Hepatitis C</condition>
  <condition>Genotype 4 Chronic Hepatitis C</condition>
  <arm_group>
    <arm_group_label>Simeprevir and Sofosbuvir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive oral capsule of Simeprevir 150 milligram (mg) along with oral tablet of sofosbuvir 400 mg, once a day from Day 1 up to Week 12.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Simeprevir</intervention_name>
    <description>Subjects will receive oral capsule of Simeprevir 150 mg, once a day from Day 1 up to Week 12.</description>
    <arm_group_label>Simeprevir and Sofosbuvir</arm_group_label>
    <other_name>TMC435</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sofosbuvir</intervention_name>
    <description>Subjects will receive oral tablet of sofosbuvir 400 mg, once a day from Day 1 up to Week 12.</description>
    <arm_group_label>Simeprevir and Sofosbuvir</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with confirmed hepatitis C virus (HCV) with HCV RNA greater than (&gt;) 10000&#xD;
             international unit per milliliter (IU/mL)&#xD;
&#xD;
          -  Subjects who are treatment naive or treatment-experienced.&#xD;
&#xD;
          -  Subjects must have documentation of a liver biopsy or fibroscan or agree to have one&#xD;
             during screening&#xD;
&#xD;
          -  Subjects with cirrhosis must have an hepatic imaging procedure (ultrasound, CT scan or&#xD;
             magnetic resonance imaging [MRI]) within 6 months before the screening visit (or&#xD;
             during the screening period) with no findings suspicious for hepatocellular carcinoma&#xD;
             (HCC)&#xD;
&#xD;
          -  Women of childbearing potential or men with a female partner of childbearing potential&#xD;
             must agree to use an effective form of contraception, or not be heterosexually active,&#xD;
             or of nonchildbearing potential&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of clinical hepatic decompensation&#xD;
&#xD;
          -  Any liver disease of non-HCV etiology&#xD;
&#xD;
          -  Subjects with a past history of treatment with an approved or investigational DAA&#xD;
&#xD;
          -  Co-infection with human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2)&#xD;
             (positive HIV-1 or HIV-2 antibodies test at screening)&#xD;
&#xD;
          -  Infection/co-infection with HCV non-genotype 4&#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>Janssen R&amp;D Ireland Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Janssen R&amp;D Ireland</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Badalona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Santander N/A</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sevilla N/A</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>September 24, 2014</study_first_submitted>
  <study_first_submitted_qc>September 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2014</study_first_posted>
  <results_first_submitted>September 28, 2016</results_first_submitted>
  <results_first_submitted_qc>September 28, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">November 17, 2016</results_first_posted>
  <last_update_submitted>September 28, 2016</last_update_submitted>
  <last_update_submitted_qc>September 28, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 17, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic hepatitis C</keyword>
  <keyword>Genotype 4 chronic hepatitis C</keyword>
  <keyword>Simeprevir</keyword>
  <keyword>Sofosbuvir</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis C, Chronic</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sofosbuvir</mesh_term>
    <mesh_term>Simeprevir</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>SMV+SOF 12 Weeks</title>
          <description>Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>SMV+SOF 12 Weeks</title>
          <description>Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51" lower_limit="29" upper_limit="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)</title>
        <description>SVR12 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (&lt;) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 12 weeks after actual EOT.</description>
        <time_frame>12 weeks after EOT</time_frame>
        <population>Intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</population>
        <group_list>
          <group group_id="O1">
            <title>SMV+SOF 12 Weeks</title>
            <description>Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)</title>
          <description>SVR12 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (&lt;) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 12 weeks after actual EOT.</description>
          <population>Intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="91.2" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Therapy (SVR4)</title>
        <description>SVR4 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (&lt;) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 4 weeks after actual EOT.</description>
        <time_frame>4 weeks after EOT</time_frame>
        <population>ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</population>
        <group_list>
          <group group_id="O1">
            <title>SMV+SOF 12 Weeks</title>
            <description>Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Therapy (SVR4)</title>
          <description>SVR4 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (&lt;) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 4 weeks after actual EOT.</description>
          <population>ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="91.2" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Therapy (SVR24)</title>
        <description>Participants were considered to have reached SVR24, if at the time point of SVR24 (that is [i.e.], 24 weeks after the end of treatment [EOT]) the following condition has been met: HCV RNA &lt; lower limit of quantification (LLOQ), i.e., 15 IU/mL, detectable or undetectable.</description>
        <time_frame>At 24 weeks after EOT</time_frame>
        <population>ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</population>
        <group_list>
          <group group_id="O1">
            <title>SMV+SOF 12 Weeks</title>
            <description>Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Therapy (SVR24)</title>
          <description>Participants were considered to have reached SVR24, if at the time point of SVR24 (that is [i.e.], 24 weeks after the end of treatment [EOT]) the following condition has been met: HCV RNA &lt; lower limit of quantification (LLOQ), i.e., 15 IU/mL, detectable or undetectable.</description>
          <population>ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="91.2" upper_limit="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)</title>
        <description>Percentage of participants with HCV RNA less than (&lt;) 15 IU/mL undetectable or detectable or detectable /undetectable at specific time points were observed.</description>
        <time_frame>Week 2, 3, 4, 12 and EOT</time_frame>
        <population>ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</population>
        <group_list>
          <group group_id="O1">
            <title>SMV+SOF 12 Weeks</title>
            <description>Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)</title>
          <description>Percentage of participants with HCV RNA less than (&lt;) 15 IU/mL undetectable or detectable or detectable /undetectable at specific time points were observed.</description>
          <population>ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 2: &lt; 100 IU/mL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="87.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2: &lt; 15 IU/mL undetectable/detectable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2: &lt; 15 IU/mL undetectable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3: &lt; 100 IU/mL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3: &lt; 15 IU/mL undetectable/detectable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3: &lt; 15 IU/mL undetectable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4: &lt; 100 IU/mL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4: &lt; 15 IU/mL undetectable/detectable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="87.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4: &lt; 15 IU/mL undetectable (RVR)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12: &lt; 100 IU/mL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12: &lt; 15 IU/mL undetectable/detectable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12: &lt; 15 IU/mL undetectable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>End of Treatment (EOT): &lt; 100 IU/mL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>EOT: &lt; 15 IU/mL undetectable/detectable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>EOT: &lt; 15 IU/mL undetectable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With On-Treatment Failure</title>
        <description>Participants were considered on-treatment failures if they have at EOT (confirmed) detectable HCV RNA, i.e., &lt;LLOQ detectable or &gt;=LLOQ.</description>
        <time_frame>through 12 weeks (EOT)</time_frame>
        <population>ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</population>
        <group_list>
          <group group_id="O1">
            <title>SMV+SOF 12 Weeks</title>
            <description>Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With On-Treatment Failure</title>
          <description>Participants were considered on-treatment failures if they have at EOT (confirmed) detectable HCV RNA, i.e., &lt;LLOQ detectable or &gt;=LLOQ.</description>
          <population>ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Viral Breakthrough</title>
        <description>Participants with confirmed &gt;1.0 log10 increase in HCV RNA from nadir or confirmed HCV RNA &gt;100 IU/mL in participants who had previously achieved HCV RNA &lt;LLOQ.</description>
        <time_frame>Up to follow-up Week 24</time_frame>
        <population>ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</population>
        <group_list>
          <group group_id="O1">
            <title>SMV+SOF 12 Weeks</title>
            <description>Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Viral Breakthrough</title>
          <description>Participants with confirmed &gt;1.0 log10 increase in HCV RNA from nadir or confirmed HCV RNA &gt;100 IU/mL in participants who had previously achieved HCV RNA &lt;LLOQ.</description>
          <population>ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Viral Relapse</title>
        <description>Participants were considered to have viral relapse if they did not achieve SVR12 and meet the following conditions: 1) at EOT, HCV RNA less than (&lt;)LLOQ, undetectable, and 2) during the follow-up period, HCV RNA greater than or equal to (&gt;=)LLOQ.</description>
        <time_frame>Up to follow-up week 24</time_frame>
        <population>ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</population>
        <group_list>
          <group group_id="O1">
            <title>SMV+SOF 12 Weeks</title>
            <description>Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Viral Relapse</title>
          <description>Participants were considered to have viral relapse if they did not achieve SVR12 and meet the following conditions: 1) at EOT, HCV RNA less than (&lt;)LLOQ, undetectable, and 2) during the follow-up period, HCV RNA greater than or equal to (&gt;=)LLOQ.</description>
          <population>ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).</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="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to EOT (Week 12)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>SMV+SOF 12 Weeks</title>
          <description>Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA Version 18.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Catarrh</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="40"/>
              </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>If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Trial Physician</name_or_title>
      <organization>Janssen R&amp;D BE</organization>
      <email>ClinicalTrialDisclosure@its.jnj.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/NCT02250807
org study id: CR105429
secondary id: TMC435HPC3021
secondary id: 2014-003446-27
nct id: NCT02250807
nct alias: NCT02256176
lead sponsor: 
has dmc: No
The purpose of this study is to show superiority of simeprevir (SMV) in combination with
      sofosbuvir for 12 weeks versus a historical control. Historical control will be a composite
      of the observed historical sustained virological response at Week 12 (SVR12) rates of SMV in
      combination with (pegylated) interferon (PegIFN)/ribavirin (RBV) of the subpopulations in
      study HPC3011 (NCT01567735) and will depend on the percentage of treatment-naive, prior
      relapser, prior non-responder, interferon (IFN)-intolerant and other subjects enrolled in
      this study.
This is a Phase 3, open-label (all people know the identity of the intervention), single-arm,
      multicenter study (conducted at multiple sites). The study consists of 3 periods: a Screening
      period (up to 4 weeks), Treatment period (12 Weeks) and Post treatment follow-up period
      (until 24 weeks after end of treatment). The duration of the subjects' participation will be
      approximately 40 weeks. In the treatment period subjects will receive oral capsule simeprevir
      along with oral tablet sofosbuvir once daily for 12 weeks. Primarily efficacy will be
      evaluated as percentage of subjects with sustained virologic response at Week 12 after the
      end of treatment. Subjects' safety will be monitored throughout the study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)
time frame: 12 weeks after EOT
description: SVR12 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 12 weeks after actual EOT.
measure: Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Therapy (SVR4)
time frame: 4 weeks after EOT
description: SVR4 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 4 weeks after actual EOT.
measure: Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Therapy (SVR24)
time frame: At 24 weeks after EOT
description: Participants were considered to have reached SVR24, if at the time point of SVR24 (that is [i.e.], 24 weeks after the end of treatment [EOT]) the following condition has been met: HCV RNA < lower limit of quantification (LLOQ), i.e., 15 IU/mL, detectable or undetectable.
measure: Percentage of Participants With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
time frame: Week 2, 3, 4, 12 and EOT
description: Percentage of participants with HCV RNA less than (<) 15 IU/mL undetectable or detectable or detectable /undetectable at specific time points were observed.
measure: Percentage of Participants With On-Treatment Failure
time frame: through 12 weeks (EOT)
description: Participants were considered on-treatment failures if they have at EOT (confirmed) detectable HCV RNA, i.e., <LLOQ detectable or >=LLOQ.
measure: Percentage of Participants With Viral Breakthrough
time frame: Up to follow-up Week 24
description: Participants with confirmed >1.0 log10 increase in HCV RNA from nadir or confirmed HCV RNA >100 IU/mL in participants who had previously achieved HCV RNA <LLOQ.
measure: Percentage of Participants With Viral Relapse
time frame: Up to follow-up week 24
description: Participants were considered to have viral relapse if they did not achieve SVR12 and meet the following conditions: 1) at EOT, HCV RNA less than (<)LLOQ, undetectable, and 2) during the follow-up period, HCV RNA greater than or equal to (>=)LLOQ.
arm group label: Simeprevir and Sofosbuvir
arm group type: Experimental
description: Subjects will receive oral capsule of Simeprevir 150 milligram (mg) along with oral tablet of sofosbuvir 400 mg, once a day from Day 1 up to Week 12.
intervention type: Drug
intervention name: Simeprevir
description: Subjects will receive oral capsule of Simeprevir 150 mg, once a day from Day 1 up to Week 12.
arm group label: Simeprevir and Sofosbuvir
other name: TMC435
intervention type: Drug
intervention name: Sofosbuvir
description: Subjects will receive oral tablet of sofosbuvir 400 mg, once a day from Day 1 up to Week 12.
arm group label: Simeprevir and Sofosbuvir
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Janssen R&D Ireland Clinical Trials
role: Study Director
affiliation: Janssen R&D Ireland
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis C, Chronic
mesh term: Virus Diseases
mesh term: Hepatitis
mesh term: Hepatitis, Chronic
mesh term: Sofosbuvir
mesh term: Simeprevir
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 