<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/NCT02252016</url>
  </required_header>
  <id_info>
    <org_study_id>5172-065</org_study_id>
    <secondary_id>2014-002356-27</secondary_id>
    <nct_id>NCT02252016</nct_id>
  </id_info>
  <brief_title>Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination for Chronic Hepatitis C Virus (HCV) Genotypes 1, 4, and 6 (MK-5172-065)</brief_title>
  <official_title>A Phase III Double Blind Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-8742 in Subjects With Chronic HCV GT1, GT4 and GT6 Infection With Inherited Blood Disorders With and Without HIV Co-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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, multi-site, placebo-controlled trial of a fixed dose combination (FDC)&#xD;
      of grazoprevir (MK-5172) 100 mg + elbasvir (MK-8742) 50 mg in participants with chronic&#xD;
      Hepatitis C Virus (HCV) genotype (GT) 1, GT4 or GT6 with inherited blood disorders. The&#xD;
      primary hypothesis is that the proportion of participants treated with grazoprevir+elbasvir&#xD;
      achieving Sustained Virologic Response (SVR) 12 weeks after the end of all study therapy&#xD;
      (SVR12) will be greater than the reference rate of 40%.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 22, 2014</start_date>
  <completion_date type="Actual">June 14, 2016</completion_date>
  <primary_completion_date type="Actual">December 7, 2015</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 Completing Study Therapy (SVR12)</measure>
    <time_frame>12 weeks after completing study therapy (Week 24)</time_frame>
    <description>The percentage of participants in the both arms achieving SVR12 (i.e., HCV riboncleic acid [RNA] level below the lower limit of quantification [LLoQ] 12 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of &lt;15 IU/mL.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Experiencing an Adverse Event (AE)</measure>
    <time_frame>Up to Week 14</time_frame>
    <description>An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Discontinuing From Study Treatment Due to an AE(s)</measure>
    <time_frame>Up to Week 12</time_frame>
    <description>An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)</measure>
    <time_frame>24 weeks after completing study therapy (Week 36)</time_frame>
    <description>The percentage of participants in both arms achieving SVR24 (i.e., HCV RNA level below the LLoQ 24 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of &lt;15 IU/mL.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">159</enrollment>
  <condition>Hepatitis C</condition>
  <arm_group>
    <arm_group_label>Immediate Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will take grazoprevir 100 mg + elbasvir 50 mg once daily during the 12-week treatment period and then will be monitored for safety during a 24-week follow-up period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Deferred Treatment</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will take placebo tablets once daily during the 12-week treatment period and will then be monitored for safety during a 4-week follow-up period. Participants will then begin open-label treatment with grazoprevir 100 mg + elbasvir 50 mg for a 12-week treatment period and will then be monitored for safety during a 24-week follow-up period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Grazoprevir + Elbasvir</intervention_name>
    <description>FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken once daily by mouth.</description>
    <arm_group_label>Deferred Treatment</arm_group_label>
    <arm_group_label>Immediate Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablets matching grazoprevir + elbasvir FDC tablets taken once daily by mouth.</description>
    <arm_group_label>Deferred Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  has HCV GT1, GT4, or GT6 with sickle cell anemia, thalassemia, or hemophilia/von&#xD;
             Willebrand disease&#xD;
&#xD;
          -  has cirrhosis or is non-cirrhotic&#xD;
&#xD;
          -  is human immunodeficiency virus (HIV) coinfected or not infected with HIV&#xD;
&#xD;
          -  is a female of non childbearing potential, or is male or female and uses an acceptable&#xD;
             method(s) of contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  has evidence of decompensated liver disease&#xD;
&#xD;
          -  is coinfected with hepatitis B&#xD;
&#xD;
          -  has had a malignancy ≤5 years prior to signing informed consent except for adequately&#xD;
             treated basal cell or squamous cell skin cancer or in situ cervical cancer&#xD;
&#xD;
          -  has hepatocellular carcinoma (HCC) or is under evaluation for HCC&#xD;
&#xD;
          -  has clinically-relevant drug or alcohol abuse within 12 months of screening&#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>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Thailand</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </removed_countries>
  <results_reference>
    <citation>Hezode C, Colombo M, Bourliere M, Spengler U, Ben-Ari Z, Strasser SI, Lee WM, Morgan L, Qiu J, Hwang P, Robertson M, Nguyen BY, Barr E, Wahl J, Haber B, Chase R, Talwani R, Marco VD; C-EDGE IBLD Study Investigators. Elbasvir/Grazoprevir for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study. Hepatology. 2017 Sep;66(3):736-745. doi: 10.1002/hep.29139. Epub 2017 Jul 20.</citation>
    <PMID>28256747</PMID>
  </results_reference>
  <verification_date>September 2018</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>November 22, 2016</results_first_submitted>
  <results_first_submitted_qc>November 22, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 19, 2017</results_first_posted>
  <last_update_submitted>September 3, 2018</last_update_submitted>
  <last_update_submitted_qc>September 3, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 3, 2018</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>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Adult participants with hepatitis C virus (HCV) genotypes (GT)1, GT4, and GT6 with inherited blood disorders and with or without human immunodeficiency virus (HIV) co-infection were recruited at study centers around the world.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Immediate Treatment</title>
          <description>Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.</description>
        </group>
        <group group_id="P2">
          <title>Deferred Treatment</title>
          <description>Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="107"/>
                <participants group_id="P2" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="104">Completed = completed 24 weeks of follow-up</participants>
                <participants group_id="P2" count="49">Completed = completed 24 weeks of follow-up</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <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="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Immediate Treatment</title>
          <description>Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.</description>
        </group>
        <group group_id="B2">
          <title>Deferred Treatment</title>
          <description>Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.</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="107"/>
            <count group_id="B2" value="52"/>
            <count group_id="B3" value="159"/>
          </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="44.2" spread="11.2"/>
                    <measurement group_id="B2" value="42.5" spread="9.8"/>
                    <measurement group_id="B3" value="43.6" spread="10.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="80"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="119"/>
                  </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 Completing Study Therapy (SVR12)</title>
        <description>The percentage of participants in the both arms achieving SVR12 (i.e., HCV riboncleic acid [RNA] level below the lower limit of quantification [LLoQ] 12 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of &lt;15 IU/mL.</description>
        <time_frame>12 weeks after completing study therapy (Week 24)</time_frame>
        <population>The Full Analysis Set (FAS) consists of all treated participants in both arms other than those who discontinued with reasons unrelated to the treatment regimen or HCV response.</population>
        <group_list>
          <group group_id="O1">
            <title>Immediate Treatment</title>
            <description>Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.</description>
          </group>
          <group group_id="O2">
            <title>Deferred Treatment</title>
            <description>Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)</title>
          <description>The percentage of participants in the both arms achieving SVR12 (i.e., HCV riboncleic acid [RNA] level below the lower limit of quantification [LLoQ] 12 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of &lt;15 IU/mL.</description>
          <population>The Full Analysis Set (FAS) consists of all treated participants in both arms other than those who discontinued with reasons unrelated to the treatment regimen or HCV response.</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="107"/>
                <count group_id="O2" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93.5" lower_limit="87.0" upper_limit="97.3"/>
                    <measurement group_id="O2" value="91.8" lower_limit="80.4" upper_limit="97.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Experiencing an Adverse Event (AE)</title>
        <description>An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.</description>
        <time_frame>Up to Week 14</time_frame>
        <population>The All-Participants-as-Treated (APaT) population includes all participants receiving ≥1 dose(s) of study drug. For the Deferred Treatment arm, data indicate results obtained during the initial 12-week placebo treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Immediate Treatment</title>
            <description>Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.</description>
          </group>
          <group group_id="O2">
            <title>Deferred Treatment</title>
            <description>Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Experiencing an Adverse Event (AE)</title>
          <description>An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.</description>
          <population>The All-Participants-as-Treated (APaT) population includes all participants receiving ≥1 dose(s) of study drug. For the Deferred Treatment arm, data indicate results obtained during the initial 12-week placebo 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="107"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.9"/>
                    <measurement group_id="O2" value="65.4"/>
                  </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>The estimated difference (± 95% confidence interval [CI]) in percentage of participants experiencing an AE in the Immediate versus Deferred arms was determined.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>7.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.3</ci_lower_limit>
            <ci_upper_limit>23.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Discontinuing From Study Treatment Due to an AE(s)</title>
        <description>An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.</description>
        <time_frame>Up to Week 12</time_frame>
        <population>The APaT population includes all participants receiving ≥1 dose(s) of study drug. For the Deferred Treatment arm, data indicate results obtained during the initial 12-week placebo treatment period.</population>
        <group_list>
          <group group_id="O1">
            <title>Immediate Treatment</title>
            <description>Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.</description>
          </group>
          <group group_id="O2">
            <title>Deferred Treatment</title>
            <description>Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Discontinuing From Study Treatment Due to an AE(s)</title>
          <description>An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.</description>
          <population>The APaT population includes all participants receiving ≥1 dose(s) of study drug. For the Deferred Treatment arm, data indicate results obtained during the initial 12-week placebo 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="107"/>
                <count group_id="O2" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="1.9"/>
                  </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>The estimated difference (± 95% CI) in percentage of participants withdrawing from study treatment due to an AE(s) in the Immediate versus Deferred arms was determined.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.155</p_value>
            <method>Miettinen &amp; Nurminen method</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.2</ci_lower_limit>
            <ci_upper_limit>1.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)</title>
        <description>The percentage of participants in both arms achieving SVR24 (i.e., HCV RNA level below the LLoQ 24 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of &lt;15 IU/mL.</description>
        <time_frame>24 weeks after completing study therapy (Week 36)</time_frame>
        <population>The FAS consists of all treated participants in both arms other than those who discontinued with reasons unrelated to the treatment regimen or HCV response.</population>
        <group_list>
          <group group_id="O1">
            <title>Immediate Treatment</title>
            <description>Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.</description>
          </group>
          <group group_id="O2">
            <title>Deferred Treatment</title>
            <description>Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)</title>
          <description>The percentage of participants in both arms achieving SVR24 (i.e., HCV RNA level below the LLoQ 24 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of &lt;15 IU/mL.</description>
          <population>The FAS consists of all treated participants in both arms other than those who discontinued with reasons unrelated to the treatment regimen or HCV response.</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="107"/>
                <count group_id="O2" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.7" lower_limit="83.5" upper_limit="95.4"/>
                    <measurement group_id="O2" value="91.8" lower_limit="80.4" upper_limit="97.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 52 weeks</time_frame>
      <desc>An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. AEs were reported for all participants receiving ≥ 1 dose of study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Immediate Treatment</title>
          <description>Participants took grazoprevir 100 mg + elbasvir 50 mg once daily (q.d.) during the initial 12-week treatment period, followed by a 24-week safety monitoring period.</description>
        </group>
        <group group_id="E2">
          <title>Deferred Treatment: Placebo Phase</title>
          <description>Participants took placebo tablets q.d. during the initial 12-week treatment period, and then underwent a 4-week safety monitoring follow-up period. Next, participants took open-label grazoprevir 100 mg + elbasvir 50 mg q.d. for 12 weeks, followed by a 24-week safety monitoring period.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA v. 19.0</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="6" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Sickle cell anaemia with crisis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastritis erosive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Osteonecrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Periarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Chronic myeloid leukaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA v. 19.0</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="78" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Haemarthrosis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="52"/>
              </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.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Glocal 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/NCT02252016
org study id: 5172-065
secondary id: 2014-002356-27
nct id: NCT02252016
lead sponsor: 
has dmc: Yes
This is a randomized, multi-site, placebo-controlled trial of a fixed dose combination (FDC)
      of grazoprevir (MK-5172) 100 mg + elbasvir (MK-8742) 50 mg in participants with chronic
      Hepatitis C Virus (HCV) genotype (GT) 1, GT4 or GT6 with inherited blood disorders. The
      primary hypothesis is that the proportion of participants treated with grazoprevir+elbasvir
      achieving Sustained Virologic Response (SVR) 12 weeks after the end of all study therapy
      (SVR12) will be greater than the reference rate of 40%.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)
time frame: 12 weeks after completing study therapy (Week 24)
description: The percentage of participants in the both arms achieving SVR12 (i.e., HCV riboncleic acid [RNA] level below the lower limit of quantification [LLoQ] 12 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of <15 IU/mL.
measure: Percentage of Participants Experiencing an Adverse Event (AE)
time frame: Up to Week 14
description: An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.
measure: Percentage of Participants Discontinuing From Study Treatment Due to an AE(s)
time frame: Up to Week 12
description: An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.
measure: Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)
time frame: 24 weeks after completing study therapy (Week 36)
description: The percentage of participants in both arms achieving SVR24 (i.e., HCV RNA level below the LLoQ 24 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of <15 IU/mL.
arm group label: Immediate Treatment
arm group type: Experimental
description: Participants will take grazoprevir 100 mg + elbasvir 50 mg once daily during the 12-week treatment period and then will be monitored for safety during a 24-week follow-up period.
arm group label: Deferred Treatment
arm group type: Placebo Comparator
description: Participants will take placebo tablets once daily during the 12-week treatment period and will then be monitored for safety during a 4-week follow-up period. Participants will then begin open-label treatment with grazoprevir 100 mg + elbasvir 50 mg for a 12-week treatment period and will then be monitored for safety during a 24-week follow-up period.
intervention type: Drug
intervention name: Grazoprevir + Elbasvir
description: FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken once daily by mouth.
arm group label: Deferred Treatment
arm group label: Immediate Treatment
intervention type: Drug
intervention name: Placebo
description: Placebo tablets matching grazoprevir + elbasvir FDC tablets taken once daily by mouth.
arm group label: Deferred Treatment
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: Canada
country: France
country: Germany
country: Greece
country: Israel
country: Italy
country: Thailand
country: United Kingdom
country: United States
citation: Hezode C, Colombo M, Bourliere M, Spengler U, Ben-Ari Z, Strasser SI, Lee WM, Morgan L, Qiu J, Hwang P, Robertson M, Nguyen BY, Barr E, Wahl J, Haber B, Chase R, Talwani R, Marco VD; C-EDGE IBLD Study Investigators. Elbasvir/Grazoprevir for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study. Hepatology. 2017 Sep;66(3):736-745. doi: 10.1002/hep.29139. Epub 2017 Jul 20.
PMID: 28256747
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis
mesh term: Grazoprevir
sharing ipd: Yes
ipd description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 