<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/NCT02251990</url>
  </required_header>
  <id_info>
    <org_study_id>5172-067</org_study_id>
    <nct_id>NCT02251990</nct_id>
  </id_info>
  <brief_title>Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination in Treatment-Naïve Hepatitis C Virus Participants (MK-5172-067)</brief_title>
  <official_title>A Phase III Randomized Multinational Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Treatment-Naïve Subjects With Chronic HCV GT 1, GT 4 and GT 6 Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</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>
      This is a randomized, parallel-group, placebo-controlled, multi-site, multinational,&#xD;
      double-blind followed by open label period, Phase 3 trial of 100 mg of grazoprevir (MK-5172)&#xD;
      in combination with 50 mg of elbasvir (MK-8742) (grazoprevir/elbasvir fixed-dose combination&#xD;
      [FDC]) in treatment-naïve (TN) participants with chronic hepatitis C virus (HCV), genotype&#xD;
      (GT) 1, 4 or 6 infection. The primary hypothesis is that the percentage of participants&#xD;
      receiving grazoprevir/elbasvir FDC in the Immediate Treatment Group (ITG) achieving Sustained&#xD;
      Virologic Response 12 weeks after the end of all study therapy (SVR12) will be superior to&#xD;
      the historical reference rate of 73%.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 28, 2015</start_date>
  <completion_date type="Actual">April 10, 2017</completion_date>
  <primary_completion_date type="Actual">September 27, 2016</primary_completion_date>
  <phase>Phase 3</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>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)</measure>
    <time_frame>12 weeks after end of all therapy (Study Week 24)</time_frame>
    <description>Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a lower limit of quantification (LLOQ) of 15 IU/mL. SVR12 was defined as HCV RNA below the lower limit of detection (&lt;LLOQ) at 12 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the primary efficacy analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Experiencing at Least One Adverse Event (AE) During the DB Treatment Period and First 14 Follow-up Days</measure>
    <time_frame>DB Treatment period plus first 14 follow-up days (up to 14 weeks)</time_frame>
    <description>An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants That Discontinued From Study Therapy Due to AEs During the DB Treatment Period</measure>
    <time_frame>DB Treatment period (up to 12 weeks)</time_frame>
    <description>An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. A participant could discontinue from treatment but continue to participate in the study as long as consent was not withdrawn. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)</measure>
    <time_frame>24 weeks after end of all therapy (Study Week 36)</time_frame>
    <description>Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR24 was defined as HCV RNA &lt;LLOQ at 24 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the secondary efficacy analysis.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Study Therapy (SVR4)</measure>
    <time_frame>4 weeks after end of all therapy (Study Week 16)</time_frame>
    <description>Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR4 was defined as HCV RNA &lt;LLOQ at 4 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in this efficacy analysis.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">489</enrollment>
  <condition>Hepatitis C</condition>
  <arm_group>
    <arm_group_label>Immediate Treatment Group (ITG): Grazoprevir/Elbasvir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive a grazoprevir/elbasvir FDC tablet once daily (q.d.) by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and are followed-up for 24 weeks to Week 36.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Deferred Treatment Group (DTG): Placebo &gt; Grazoprevir/Elbasvir</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants receive a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants receive open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants are then followed-up for 24 weeks to Week 52.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Grazoprevir/Elbasvir</intervention_name>
    <description>FDC tablet containing 100 mg of grazoprevir and 50 mg of elbasvir taken q.d. by mouth for 12 weeks.</description>
    <arm_group_label>Immediate Treatment Group (ITG): Grazoprevir/Elbasvir</arm_group_label>
    <other_name>MK-5172A</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablet matching grazoprevir/elbasvir FDC tablet taken q.d. by mouth for 12 weeks.</description>
    <arm_group_label>Deferred Treatment Group (DTG): Placebo &gt; Grazoprevir/Elbasvir</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has documented chronic HCV GT1, GT4, or GT6 (with no evidence of non-typeable or mixed&#xD;
             genotype) infection&#xD;
&#xD;
          -  Meets clinical criteria for presence or absence of cirrhosis based on liver disease&#xD;
             staging assessment&#xD;
&#xD;
          -  Is abstinent or uses acceptable method(s) of contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has evidence of decompensated liver disease&#xD;
&#xD;
          -  Is coinfected with hepatitis B virus or human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Shows evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC&#xD;
&#xD;
          -  Has a clinically-relevant drug or alcohol abuse within 12 months of screening&#xD;
&#xD;
          -  Is pregnant or breast-feeding&#xD;
&#xD;
          -  Has any condition or abnormality that might confound the results of the trial or pose&#xD;
             an additional risk to the participant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>Australia</country>
    <country>China</country>
    <country>Korea, Republic of</country>
    <country>Russian Federation</country>
    <country>Taiwan</country>
    <country>Thailand</country>
    <country>Vietnam</country>
  </removed_countries>
  <reference>
    <citation>Wei L, Jia JD, Wang FS, Niu JQ, Zhao XM, Mu S, Liang LW, Wang Z, Hwang P, Robertson MN, Ingravallo P, Asante-Appiah E, Wei B, Evans B, Hanna GJ, Talwani R, Duan ZP, Zhdanov K, Cheng PN, Tanwandee T, Nguyen VK, Heo J, Isakov V, George J; C-CORAL Investigators. Efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1, 4, or 6 infection from the Asia-Pacific region and Russia: Final results from the randomized C-CORAL study. J Gastroenterol Hepatol. 2019 Jan;34(1):12-21. doi: 10.1111/jgh.14509. Epub 2018 Dec 9.</citation>
    <PMID>30311701</PMID>
  </reference>
  <results_reference>
    <citation>George J, Burnevich E, Sheen IS, Heo J, Kinh NV, Tanwandee T, Cheng PN, Kim DY, Tak WY, Kizhlo S, Zhdanov K, Isakov V, Liang L, Lindore P, Ginanni J, Nguyen BY, Wahl J, Barr E, Robertson M, Ingravallo P, Talwani R; C-CORAL Study Investigators. Elbasvir/grazoprevir in Asia-Pacific/Russian participants with chronic hepatitis C virus genotype 1, 4, or 6 infection. Hepatol Commun. 2018 Apr 4;2(5):595-606. doi: 10.1002/hep4.1177. eCollection 2018 May.</citation>
    <PMID>29761174</PMID>
  </results_reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>September 25, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <results_first_submitted>September 18, 2017</results_first_submitted>
  <results_first_submitted_qc>September 18, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">October 17, 2017</results_first_posted>
  <last_update_submitted>January 11, 2019</last_update_submitted>
  <last_update_submitted_qc>January 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Grazoprevir</mesh_term>
    <mesh_term>Elbasvir-grazoprevir drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>For Subject Disposition, Period 1 covers Day 1 through Week 12 for both treatment groups. Period 2 covers Week 12 through Week 36 for the Immediate Treatment Group (ITG) and Week 12 through Week 28 for the Deferred Treatment Group (DTG). Period 3 covers Week 28 through Week 52 for the DTG; the ITG completed the study with Period 2.</recruitment_details>
      <pre_assignment_details>A total of 489 participants were randomized to treatment, and 488 participants received ≥1 dose of study drug during the blinded period. One participant randomized to the ITG withdrew consent after randomization, but prior to receiving study drug.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Immediate Treatment Group (ITG): Grazoprevir/Elbasvir</title>
          <description>Participants received a grazoprevir/elbasvir fixed-dose combination (FDC) tablet once daily (q.d.) by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.</description>
        </group>
        <group group_id="P2">
          <title>Deferred Treatment Group (DTG): Placebo &gt; Grazoprevir/Elbasvir</title>
          <description>Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1 (Double-blind [DB])</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="366"/>
                <participants group_id="P2" count="123"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="365">Started Grazoprevir/Elbasvir</participants>
                <participants group_id="P2" count="123">Started Placebo</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="358">Completed 12 weeks of Grazoprevir/Elbasvir</participants>
                <participants group_id="P2" count="122">Completed 12 weeks of Placebo</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Not Treated</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 2 (ITG Follow-up/DTG Open Label)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="360">2 participants that did not complete Period 1 treatment were included in Follow-up.</participants>
                <participants group_id="P2" count="121">1 participant completing Period 1 was not eligible for Period 2 and was not treated.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="360">Completed 24 weeks of follow-up</participants>
                <participants group_id="P2" count="118">Completed 12 weeks of Grazoprevir/Elbasvir</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 3 (DTG Follow-up)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0">The ITG completed the study with Period 2</participants>
                <participants group_id="P2" count="121">3 participants that discontinued treatment in Period 2 were included in Follow-up.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="121">Completed 24 weeks of follow-up</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All randomized participants who received at least one dose of study treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Immediate Treatment Group (ITG): Grazoprevir/Elbasvir</title>
          <description>Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.</description>
        </group>
        <group group_id="B2">
          <title>Deferred Treatment Group (DTG): Placebo &gt; Grazoprevir/Elbasvir</title>
          <description>Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="365"/>
            <count group_id="B2" value="123"/>
            <count group_id="B3" value="488"/>
          </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="48.1" spread="12.9"/>
                    <measurement group_id="B2" value="48.6" spread="12.9"/>
                    <measurement group_id="B3" value="48.3" spread="12.9"/>
                  </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="205"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="272"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="160"/>
                    <measurement group_id="B2" value="56"/>
                    <measurement group_id="B3" value="216"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)</title>
        <description>Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a lower limit of quantification (LLOQ) of 15 IU/mL. SVR12 was defined as HCV RNA below the lower limit of detection (&lt;LLOQ) at 12 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the primary efficacy analysis.</description>
        <time_frame>12 weeks after end of all therapy (Study Week 24)</time_frame>
        <population>All randomized participants in the Immediate Treatment Group who received at least one dose of study treatment. The Deferred Treatment Group was not included in the primary efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Immediate Treatment Group (ITG): Grazoprevir/Elbasvir</title>
            <description>Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.</description>
          </group>
          <group group_id="O2">
            <title>Deferred Treatment Group (DTG): Placebo &gt; Grazoprevir/Elbasvir</title>
            <description>Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)</title>
          <description>Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a lower limit of quantification (LLOQ) of 15 IU/mL. SVR12 was defined as HCV RNA below the lower limit of detection (&lt;LLOQ) at 12 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the primary efficacy analysis.</description>
          <population>All randomized participants in the Immediate Treatment Group who received at least one dose of study treatment. The Deferred Treatment Group was not included in the primary efficacy analysis.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>97.5% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="365"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.2" lower_limit="91.5" upper_limit="97.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>A one-sided Wald test was used to test the null hypothesis, which was that the SVR12 rate for the ITG was ≤ the historical reference rate of 73%. The historical reference SVR rate for treatment-naive genotype 1 predominantly Asian participants treated with pegylated interferon/ribavirin was derived from 2 studies (PMCID: PMC417, PMCID: PMC3644280) after adjusting for an expected improved safety profile related to an interferon-free regimen.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>The p-value was based on a one-sided asymptotic test for a binomial proportion. A one-sided p-value &lt;0.0125 was considered supportive of a conclusion that the true SVR12 is &gt;73%.</p_value_desc>
            <method>one-sided asymptotic test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Experiencing at Least One Adverse Event (AE) During the DB Treatment Period and First 14 Follow-up Days</title>
        <description>An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.</description>
        <time_frame>DB Treatment period plus first 14 follow-up days (up to 14 weeks)</time_frame>
        <population>All randomized participants who received at least one dose of study treatment during the double-blind treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Immediate Treatment Group (ITG): Grazoprevir/Elbasvir</title>
            <description>Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.</description>
          </group>
          <group group_id="O2">
            <title>Deferred Treatment Group (DTG): Placebo &gt; Grazoprevir/Elbasvir</title>
            <description>Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Experiencing at Least One Adverse Event (AE) During the DB Treatment Period and First 14 Follow-up Days</title>
          <description>An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.</description>
          <population>All randomized participants who received at least one dose of study treatment during the double-blind treatment period.</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="365"/>
                <count group_id="O2" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.7"/>
                    <measurement group_id="O2" value="51.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Estimates and 95% CIs were calculated for between-treatment differences (ITG minus DTG) in the percentage of participants with events using the Miettinen and Nurminen method.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Difference in Percentages</param_type>
            <param_value>-0.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.6</ci_lower_limit>
            <ci_upper_limit>9.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants That Discontinued From Study Therapy Due to AEs During the DB Treatment Period</title>
        <description>An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. A participant could discontinue from treatment but continue to participate in the study as long as consent was not withdrawn. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.</description>
        <time_frame>DB Treatment period (up to 12 weeks)</time_frame>
        <population>All randomized participants who received at least one dose of study treatment during the double-blind treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Immediate Treatment Group (ITG): Grazoprevir/Elbasvir</title>
            <description>Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.</description>
          </group>
          <group group_id="O2">
            <title>Deferred Treatment Group (DTG): Placebo &gt; Grazoprevir/Elbasvir</title>
            <description>Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants That Discontinued From Study Therapy Due to AEs During the DB Treatment Period</title>
          <description>An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. A participant could discontinue from treatment but continue to participate in the study as long as consent was not withdrawn. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.</description>
          <population>All randomized participants who received at least one dose of study treatment during the double-blind treatment period.</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="365"/>
                <count group_id="O2" value="123"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3"/>
                    <measurement group_id="O2" value="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Estimates and 95% CIs were calculated for between-treatment differences (ITG minus DTG) in the percentage of participants with events using the Miettinen and Nurminen method.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Difference in Percentages</param_type>
            <param_value>-0.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.2</ci_lower_limit>
            <ci_upper_limit>0.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)</title>
        <description>Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR24 was defined as HCV RNA &lt;LLOQ at 24 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the secondary efficacy analysis.</description>
        <time_frame>24 weeks after end of all therapy (Study Week 36)</time_frame>
        <population>All randomized participants in the Immediate Treatment Group who received at least one dose of study treatment. The Deferred Treatment Group was not included in the secondary efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Immediate Treatment Group (ITG): Grazoprevir/Elbasvir</title>
            <description>Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.</description>
          </group>
          <group group_id="O2">
            <title>Deferred Treatment Group (DTG): Placebo &gt; Grazoprevir/Elbasvir</title>
            <description>Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)</title>
          <description>Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR24 was defined as HCV RNA &lt;LLOQ at 24 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the secondary efficacy analysis.</description>
          <population>All randomized participants in the Immediate Treatment Group who received at least one dose of study treatment. The Deferred Treatment Group was not included in the secondary efficacy analysis.</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="365"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.0" lower_limit="91.5" upper_limit="96.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Study Therapy (SVR4)</title>
        <description>Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR4 was defined as HCV RNA &lt;LLOQ at 4 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in this efficacy analysis.</description>
        <time_frame>4 weeks after end of all therapy (Study Week 16)</time_frame>
        <population>All randomized participants in the Immediate Treatment Group who received at least one dose of study treatment. The Deferred Treatment Group was not included in this efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Immediate Treatment Group (ITG): Grazoprevir/Elbasvir</title>
            <description>Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.</description>
          </group>
          <group group_id="O2">
            <title>Deferred Treatment Group (DTG): Placebo &gt; Grazoprevir/Elbasvir</title>
            <description>Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Study Therapy (SVR4)</title>
          <description>Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR4 was defined as HCV RNA &lt;LLOQ at 4 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in this efficacy analysis.</description>
          <population>All randomized participants in the Immediate Treatment Group who received at least one dose of study treatment. The Deferred Treatment Group was not included in this efficacy analysis.</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="365"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.2" lower_limit="94.2" upper_limit="98.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52</time_frame>
      <desc>All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.</desc>
      <group_list>
        <group group_id="E1">
          <title>Immediate Treatment Group (ITG): Grazoprevir/Elbasvir</title>
          <description>Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36</description>
        </group>
        <group group_id="E2">
          <title>Deferred Treatment Group (DTG): Placebo</title>
          <description>Participants received a placebo tablet q.d. by mouth for 12 weeks during the double-blind treatment period (Weeks 1 to 12). Participants were then followed-up for 4 weeks to Week 16.</description>
        </group>
        <group group_id="E3">
          <title>Deferred Treatment Group (DTG): Grazoprevir/Elbasvir</title>
          <description>Participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="365"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Evans syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Enteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="121"/>
              </event>
              <event>
                <sub_title>Irritable bowel syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="121"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="121"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="365"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="121"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="121"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="121"/>
              </event>
              <event>
                <sub_title>Foot fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="365"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="121"/>
              </event>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Lymphoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Completed suicide</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Uterine polyp</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="365"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="123"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="121"/>
              </event>
              <event>
                <sub_title>Uterine haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="365"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.0</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="85" subjects_at_risk="365"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="21" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="22" subjects_affected="21" subjects_at_risk="365"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="123"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="21" subjects_affected="21" subjects_at_risk="365"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="123"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="30" subjects_affected="26" subjects_at_risk="365"/>
                <counts group_id="E2" events="9" subjects_affected="8" subjects_at_risk="123"/>
                <counts group_id="E3" events="10" subjects_affected="10" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="365"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="123"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="121"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="365"/>
                <counts group_id="E2" events="9" subjects_affected="7" subjects_at_risk="123"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="24" subjects_affected="24" subjects_at_risk="365"/>
                <counts group_id="E2" events="11" subjects_affected="6" subjects_at_risk="123"/>
                <counts group_id="E3" events="9" subjects_affected="6" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme Corp.</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.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/NCT02251990
org study id: 5172-067
nct id: NCT02251990
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized, parallel-group, placebo-controlled, multi-site, multinational,
      double-blind followed by open label period, Phase 3 trial of 100 mg of grazoprevir (MK-5172)
      in combination with 50 mg of elbasvir (MK-8742) (grazoprevir/elbasvir fixed-dose combination
      [FDC]) in treatment-naïve (TN) participants with chronic hepatitis C virus (HCV), genotype
      (GT) 1, 4 or 6 infection. The primary hypothesis is that the percentage of participants
      receiving grazoprevir/elbasvir FDC in the Immediate Treatment Group (ITG) achieving Sustained
      Virologic Response 12 weeks after the end of all study therapy (SVR12) will be superior to
      the historical reference rate of 73%.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)
time frame: 12 weeks after end of all therapy (Study Week 24)
description: Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a lower limit of quantification (LLOQ) of 15 IU/mL. SVR12 was defined as HCV RNA below the lower limit of detection (<LLOQ) at 12 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the primary efficacy analysis.
measure: Percentage of Participants Experiencing at Least One Adverse Event (AE) During the DB Treatment Period and First 14 Follow-up Days
time frame: DB Treatment period plus first 14 follow-up days (up to 14 weeks)
description: An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.
measure: Percentage of Participants That Discontinued From Study Therapy Due to AEs During the DB Treatment Period
time frame: DB Treatment period (up to 12 weeks)
description: An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. A participant could discontinue from treatment but continue to participate in the study as long as consent was not withdrawn. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.
measure: Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)
time frame: 24 weeks after end of all therapy (Study Week 36)
description: Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR24 was defined as HCV RNA <LLOQ at 24 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the secondary efficacy analysis.
measure: Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Study Therapy (SVR4)
time frame: 4 weeks after end of all therapy (Study Week 16)
description: Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR4 was defined as HCV RNA <LLOQ at 4 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in this efficacy analysis.
arm group label: Immediate Treatment Group (ITG): Grazoprevir/Elbasvir
arm group type: Experimental
description: Participants receive a grazoprevir/elbasvir FDC tablet once daily (q.d.) by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and are followed-up for 24 weeks to Week 36.
arm group label: Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir
arm group type: Placebo Comparator
description: Participants receive a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants receive open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants are then followed-up for 24 weeks to Week 52.
intervention type: Drug
intervention name: Grazoprevir/Elbasvir
description: FDC tablet containing 100 mg of grazoprevir and 50 mg of elbasvir taken q.d. by mouth for 12 weeks.
arm group label: Immediate Treatment Group (ITG): Grazoprevir/Elbasvir
other name: MK-5172A
intervention type: Drug
intervention name: Placebo
description: Placebo tablet matching grazoprevir/elbasvir FDC tablet taken q.d. by mouth for 12 weeks.
arm group label: Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
country: Australia
country: China
country: Korea, Republic of
country: Russian Federation
country: Taiwan
country: Thailand
country: Vietnam
citation: Wei L, Jia JD, Wang FS, Niu JQ, Zhao XM, Mu S, Liang LW, Wang Z, Hwang P, Robertson MN, Ingravallo P, Asante-Appiah E, Wei B, Evans B, Hanna GJ, Talwani R, Duan ZP, Zhdanov K, Cheng PN, Tanwandee T, Nguyen VK, Heo J, Isakov V, George J; C-CORAL Investigators. Efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1, 4, or 6 infection from the Asia-Pacific region and Russia: Final results from the randomized C-CORAL study. J Gastroenterol Hepatol. 2019 Jan;34(1):12-21. doi: 10.1111/jgh.14509. Epub 2018 Dec 9.
PMID: 30311701
citation: George J, Burnevich E, Sheen IS, Heo J, Kinh NV, Tanwandee T, Cheng PN, Kim DY, Tak WY, Kizhlo S, Zhdanov K, Isakov V, Liang L, Lindore P, Ginanni J, Nguyen BY, Wahl J, Barr E, Robertson M, Ingravallo P, Talwani R; C-CORAL Study Investigators. Elbasvir/grazoprevir in Asia-Pacific/Russian participants with chronic hepatitis C virus genotype 1, 4, or 6 infection. Hepatol Commun. 2018 Apr 4;2(5):595-606. doi: 10.1002/hep4.1177. eCollection 2018 May.
PMID: 29761174
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis
mesh term: Grazoprevir
mesh term: Elbasvir-grazoprevir drug combination
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 