<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/NCT01724086</url>
  </required_header>
  <id_info>
    <org_study_id>CR100882</org_study_id>
    <secondary_id>TMC647055HPC2001</secondary_id>
    <secondary_id>2012-002555-42</secondary_id>
    <nct_id>NCT01724086</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety, Tolerability, and Effectiveness of a 12-Week Combination Therapy of TMC647055 and TMC435 With and Without GSK23336805 With a Pharmacokinetic Enhancer With and Without Ribavirin in Patients Infected With Chronic Genotype 1 Hepatitis C Virus</brief_title>
  <official_title>A Phase IIa, Open-label Trial to Evaluate the Safety, Tolerability and Efficacy of a 12 Weeks Combination Therapy of TMC647055 and TMC435 With and Without GSK23336805 With a Pharmacokinetic Enhancer With and Without Ribavirin in Chronic Genotype 1 Hepatitis C Infected Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen R&amp;D Ireland</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen R&amp;D Ireland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to explore the efficacy and safety of TMC647055, TMC435, and&#xD;
      low-dose ritonavir, administered together with and without ribavirin and of TMC647055,&#xD;
      TMC435, low-dose ritonavir administered together with GSK233680k without ribavirin in a&#xD;
      limited number of patients with chronic hepatitis C virus (HCV) infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is an open-label study (all people know the identity of the intervention) in&#xD;
      patients who are chronically infected with hepatitis C virus (HCV) genotype-1a (GT1a) or&#xD;
      genotype-1b (GT1b) to assess the safety, tolerability and efficacy of the coadministration of&#xD;
      TMC647055, TMC435 and low-dose ritonavir (RTV), with and without ribavirin (RBV) and of&#xD;
      TMC647055, TMC435, RTV administered together with GSK233680k without RBV for 12 weeks.&#xD;
      Approximately 86 patients will be enrolled in this study. Patients enrolled in the study will&#xD;
      be chronically infected with HCV of GT1a (n=10) or GT1b (n=20), either treatment-naive&#xD;
      patients (ie, patients never having received PegIFN [Pegylated interferon alpha-2a at 180 mcg&#xD;
      subcutaneous once a week], RBV, or any other approved or investigational treatment for&#xD;
      chronic HCV infection) or patients who are relapsers to prior treatment with PegIFN /RBV (ie,&#xD;
      &quot;relapsers&quot; are patients with HCV ribonucleic acid [RNA] undetectable at the last on&#xD;
      treatment measurement of a prior PegIFN based regimen of at least 24 weeks, but HCV RNA&#xD;
      detectable within 1 year after the last medication intake). Patients in this first part of&#xD;
      the study will be divided over 4 panels: Panel 1 will consist of 10 chronic HCV GT1a infected&#xD;
      treatment-naive patients/prior relapsers who will receive 12 weeks of treatment with TMC435 +&#xD;
      TMC647055 + low-dose ritonavir and ribavirin. Panel 2 will consist of 20 chronic HCV GT1b&#xD;
      infected treatment-naive patients/ prior relapsers who will be randomly allocated to 2 arms&#xD;
      in a 1:1 ratio. Arm 1 (N=10) will receive TMC435 + TMC647055 + low-dose ritonavir and&#xD;
      ribavirin. Arm 2 (N=10) will receive TMC435 + TMC647055 + low-dose ritonavir. Panel 3 will&#xD;
      consist of 16 chronic HCV GT1a or GT1b infected treatment-naïve patients/prior relapsers who&#xD;
      will be allocated to 2 arms: 8 HCV GT1a patients in arm 1 and 8 HCV GT1b patients in arm 2.&#xD;
      Patients in Arm 1 will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose RTV&#xD;
      and RBV and patients in Arm 2 will receive 12 weeks of treatment with TMC435 + TMC647055 +&#xD;
      low-dose RTV. Panel 4 will consist of 40 chronic HCV GT1a or GT1b infected treatment-naïve&#xD;
      patients/prior relapsers who will be allocated to 2 arms: each arm will consist of 20&#xD;
      patients of which at most 8 patients will be infected with HCV GT1b. Patients will be&#xD;
      randomized in 1:1 ratio between the 2 arms whereby randomization will be stratified by&#xD;
      genotype. Patients in Arm 1 will receive 12 weeks of treatment with TMC435 + TMC647055 +&#xD;
      low-dose RTV + GSK2336805. Patients in Arm 2 will receive 12 weeks of treatment with TMC435 +&#xD;
      TMC647055 + low-dose RTV + GSK2336805. The planned duration of the investigational treatment&#xD;
      is 12 weeks. Patients in Panels 1, 2, and 3 may receive follow-up treatment with 12 weeks or&#xD;
      36 weeks of PegIFNα + RBV; follow-up treatment principles will not apply to Panel 4 as based&#xD;
      on available proof of concept data for such combinations, the need for an additional 12 or&#xD;
      36-week PegIFN/RBV follow-up therapy is expected to be very low when evaluating a 12-week&#xD;
      regimen of 3 direct acting antiviral agents for treatment of HCV genotype 1 infections.&#xD;
      Safety will be monitored throughout the study&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with a sustained virologic response (SVR) 12 Weeks after the actual end of treatment</measure>
    <time_frame>Week 24 (Up to 12 weeks after end-of treatment visit)</time_frame>
    <description>SVR12 is defined as undetectable HCV RNA at the actual end of treatment and HCV RNA less than 25 IU/mL at 12 Weeks after the actual end of treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to Week 48 (24 weeks after end of treatment)</time_frame>
    <description>Number of patients with adverse events, serious adverse events, abnormal changes in safety related laboratory values, abnormal changes in vital signs and physical examination, and abnormal echocardiogram.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with a sustained virological response (SVR at 4 and/or 24 Weeks after the actual end of treatment)</measure>
    <time_frame>Up to 24 weeks after end of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HCV RNA levels over time</measure>
    <time_frame>Up to 24 weeks after end of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with undetectable hepatitis C virus (HCV) RNA (less than 25 IU/mL undetectable) and/or HCV RNA levels less than 25 IU/mL at all time points</measure>
    <time_frame>Up to 24 weeks after end of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with on-treatment virologic failure</measure>
    <time_frame>End of treatment (Week 48)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with viral relapse</measure>
    <time_frame>Up to 24 weeks after end of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with presence of HCV variants associated with reduced susceptibility to investigational treatment</measure>
    <time_frame>Up to 24 weeks after end of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma analyte concentration of TMC435</measure>
    <time_frame>Week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum plasma analyte concentration of TMC435</measure>
    <time_frame>Week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve of TMC435</measure>
    <time_frame>Week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma analyte concentration of TMC647055</measure>
    <time_frame>Week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum plasma analyte concentration of TMC647055</measure>
    <time_frame>Week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve of TMC647055</measure>
    <time_frame>Week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma analyte concentration of ritonavir (RTV)</measure>
    <time_frame>Week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum plasma analyte concentration of RTV</measure>
    <time_frame>Week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve of RTV</measure>
    <time_frame>Week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum and maximum plasma concentrations of GSK233680k</measure>
    <time_frame>Week 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve of GSK233680k</measure>
    <time_frame>Week 4</time_frame>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Chronic Hepatitis C</condition>
  <arm_group>
    <arm_group_label>Panel 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 chronic HCV genotype 1a (GT1a) infected treatment-naive patients/prior relapsers who will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose ritonavir and ribavirin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel 2 Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir and ribavirin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel 2 Arm 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel 3 - Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 chronic HCV GT1a infected treatment naïve patients/prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir + ribavirin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel 3 - Arm 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8 chronically HCV GT1b infected treatment naïve patients/prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel 4 - Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 chronic HCV GT1a or GT1b infected treatment-naive patients/ prior relapsers will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose RTV + GSK2336805 (30 mg once daily)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Panel 4 - Arm 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 chronic HCV GT1a or GT1b infected treatment-naive patients/ prior relapsers will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose RTV + GSK2336805 (60 mg once daily)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TMC647055</intervention_name>
    <description>Type=exact number, unit=mg, number=150, form=capsule, route=oral. 3 or 4 capsules of 150 mg will be administered once daily.</description>
    <arm_group_label>Panel 1</arm_group_label>
    <arm_group_label>Panel 2 Arm 1</arm_group_label>
    <arm_group_label>Panel 2 Arm 2</arm_group_label>
    <arm_group_label>Panel 3 - Arm 1</arm_group_label>
    <arm_group_label>Panel 3 - Arm 2</arm_group_label>
    <arm_group_label>Panel 4 - Arm 1</arm_group_label>
    <arm_group_label>Panel 4 - Arm 2</arm_group_label>
    <other_name>JNJ-42039556-AMR-G-001</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TMC435</intervention_name>
    <description>Type=exact number, unit=mg, number=75, form=capsule, route=oral. 1 capsule of 75 mg will be administered once daily.</description>
    <arm_group_label>Panel 1</arm_group_label>
    <arm_group_label>Panel 2 Arm 1</arm_group_label>
    <arm_group_label>Panel 2 Arm 2</arm_group_label>
    <arm_group_label>Panel 3 - Arm 1</arm_group_label>
    <arm_group_label>Panel 3 - Arm 2</arm_group_label>
    <arm_group_label>Panel 4 - Arm 1</arm_group_label>
    <arm_group_label>Panel 4 - Arm 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ritonavir</intervention_name>
    <description>Type=exact number, unit=mg, number=30 or 50, form=tablet or solution, route=oral. 0.375 mL or 0.625 ml (80 mg/mL) solution will be administered once daily.</description>
    <arm_group_label>Panel 1</arm_group_label>
    <arm_group_label>Panel 2 Arm 1</arm_group_label>
    <arm_group_label>Panel 2 Arm 2</arm_group_label>
    <arm_group_label>Panel 3 - Arm 1</arm_group_label>
    <arm_group_label>Panel 3 - Arm 2</arm_group_label>
    <arm_group_label>Panel 4 - Arm 1</arm_group_label>
    <arm_group_label>Panel 4 - Arm 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ribavirin</intervention_name>
    <description>Type=exact number, unit=mg, number=200, form=tablet, route=oral. 5 to 6 (1000 or 1200 mg) tablets will be administered once daily, divided in 2 daily doses. Patients meeting the Follow-UP (FU) treatment criteria specified in the protocol will receive treatment 5 or 6 (depending on bodyweight) tablets of ribavirin (equivalent to 200 mg/tablet) per day, divided in 2 daily doses for an additional 12 or 36 weeks.</description>
    <arm_group_label>Panel 1</arm_group_label>
    <arm_group_label>Panel 2 Arm 1</arm_group_label>
    <arm_group_label>Panel 2 Arm 2</arm_group_label>
    <arm_group_label>Panel 3 - Arm 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegylated interferon alpha-2a (PegIFN)</intervention_name>
    <description>Type=exact number, unit=mcg, number=180, form=solution, route=subcutaneous injection. PegIFN 0.5 mL prefilled syringe equivalent to 180 mcg will be administered as a subcutaneous (under the skin) injection as follow-up (FU) treatment for 12 or 36 weeks based on follow-up treatment principles as described in the protocol. Patients meeting the Follow-UP (FU) treatment criteria specified in the protocol will receive treatment with Pegylated interferon alpha-2a (PegIFN) 0.5 mL prefilled syringe equivalent to 180 mcg administered as a subcutaneous (under the skin) injection for an additional 12 or 36 weeks.</description>
    <arm_group_label>Panel 1</arm_group_label>
    <arm_group_label>Panel 2 Arm 1</arm_group_label>
    <arm_group_label>Panel 2 Arm 2</arm_group_label>
    <arm_group_label>Panel 3 - Arm 1</arm_group_label>
    <arm_group_label>Panel 3 - Arm 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK2336805</intervention_name>
    <description>Type=exact number, unit=mg, number=30 or 60, form=tablet, route=subcutaneous injection. GSK2336805 one or two 30 mg tablet(s) taken orally (by mouth) once daily for 12 weeks.</description>
    <arm_group_label>Panel 4 - Arm 1</arm_group_label>
    <arm_group_label>Panel 4 - Arm 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented chronic genotype 1a or genotype 1b hepatitis C virus (HCV) infection with&#xD;
             HCV ribonucleic acid (RNA) level &gt;100,000 IU/mL at screening&#xD;
&#xD;
          -  Treatment-naive or documented prior relapser to previous treatment regimens and has&#xD;
             stopped treatment at least 3 months before screening&#xD;
&#xD;
          -  Liver biopsy within 3 years before the screening visit or elastography results&#xD;
             available prior to first study drug dosing&#xD;
&#xD;
          -  Medically stable based on physical examination, medical history, vital signs, and&#xD;
             electrocardiogram performed at screening&#xD;
&#xD;
          -  Body mass index of 18.0 to 32.0 kg/m2 and body weight more than 50 kg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of liver cirrhosis by liver biopsy or the presence of esophageal varices or a&#xD;
             transient elastography result of &gt;14.6 kPa within 2 years prior to first dosing&#xD;
&#xD;
          -  Evidence of decompensated liver disease defined as prior history or current evidence&#xD;
             of ascites, hepatic encephalopathy, bleeding oesophageal or gastric varices&#xD;
&#xD;
          -  Evidence of any significant liver disease in addition to hepatitis C (including but&#xD;
             not limited to hepatitis B, drug- or alcohol-related cirrhosis, autoimmune hepatitis,&#xD;
             hemochromatosis, Wilson's disease, non-alcoholic steatohepatitis, or primary biliary&#xD;
             cirrhosis)&#xD;
&#xD;
          -  Receiving or has received any HCV-specific direct antiviral agent (HCV protease&#xD;
             inhibitors, HCV nucleoside polymerase inhibitors, HCV non-nucleoside polymerase&#xD;
             inhibitors, HCV NS5a inhibitors or any other HCV inhibitor targeting an HCV protein or&#xD;
             a target involved in the HCV replication cycle&#xD;
&#xD;
          -  Co-infected with human immunovirus (HIV)-1 or HIV-2, with non-genotype 1a/1b HCV, or&#xD;
             hepatitis A or B virus infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen R&amp;D Ireland Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen R&amp;D Ireland</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Antwerpen</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Brugge</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Edegem</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Liège</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Mainz</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Germany</country>
  </location_countries>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>September 26, 2012</study_first_submitted>
  <study_first_submitted_qc>November 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 9, 2012</study_first_posted>
  <last_update_submitted>January 8, 2016</last_update_submitted>
  <last_update_submitted_qc>January 8, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 11, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic hepatitis C</keyword>
  <keyword>Chronic hepatitis C-infected patients</keyword>
  <keyword>TMC647055</keyword>
  <keyword>TMC435</keyword>
  <keyword>Ritonavir</keyword>
  <keyword>Ribavirin</keyword>
  <keyword>Genotype 1a</keyword>
  <keyword>Genotype 1b</keyword>
  <keyword>GSK2336805</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis C, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interferons</mesh_term>
    <mesh_term>Ritonavir</mesh_term>
    <mesh_term>Ribavirin</mesh_term>
    <mesh_term>Interferon-alpha</mesh_term>
    <mesh_term>Interferon alpha-2</mesh_term>
    <mesh_term>Peginterferon alfa-2a</mesh_term>
    <mesh_term>Simeprevir</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01724086
org study id: CR100882
secondary id: TMC647055HPC2001
secondary id: 2012-002555-42
nct id: NCT01724086
lead sponsor: 
has dmc: No
The purpose of this study is to explore the efficacy and safety of TMC647055, TMC435, and
      low-dose ritonavir, administered together with and without ribavirin and of TMC647055,
      TMC435, low-dose ritonavir administered together with GSK233680k without ribavirin in a
      limited number of patients with chronic hepatitis C virus (HCV) infection.
This study is an open-label study (all people know the identity of the intervention) in
      patients who are chronically infected with hepatitis C virus (HCV) genotype-1a (GT1a) or
      genotype-1b (GT1b) to assess the safety, tolerability and efficacy of the coadministration of
      TMC647055, TMC435 and low-dose ritonavir (RTV), with and without ribavirin (RBV) and of
      TMC647055, TMC435, RTV administered together with GSK233680k without RBV for 12 weeks.
      Approximately 86 patients will be enrolled in this study. Patients enrolled in the study will
      be chronically infected with HCV of GT1a (n=10) or GT1b (n=20), either treatment-naive
      patients (ie, patients never having received PegIFN [Pegylated interferon alpha-2a at 180 mcg
      subcutaneous once a week], RBV, or any other approved or investigational treatment for
      chronic HCV infection) or patients who are relapsers to prior treatment with PegIFN /RBV (ie,
      "relapsers" are patients with HCV ribonucleic acid [RNA] undetectable at the last on
      treatment measurement of a prior PegIFN based regimen of at least 24 weeks, but HCV RNA
      detectable within 1 year after the last medication intake). Patients in this first part of
      the study will be divided over 4 panels: Panel 1 will consist of 10 chronic HCV GT1a infected
      treatment-naive patients/prior relapsers who will receive 12 weeks of treatment with TMC435 +
      TMC647055 + low-dose ritonavir and ribavirin. Panel 2 will consist of 20 chronic HCV GT1b
      infected treatment-naive patients/ prior relapsers who will be randomly allocated to 2 arms
      in a 1:1 ratio. Arm 1 (N=10) will receive TMC435 + TMC647055 + low-dose ritonavir and
      ribavirin. Arm 2 (N=10) will receive TMC435 + TMC647055 + low-dose ritonavir. Panel 3 will
      consist of 16 chronic HCV GT1a or GT1b infected treatment-naïve patients/prior relapsers who
      will be allocated to 2 arms: 8 HCV GT1a patients in arm 1 and 8 HCV GT1b patients in arm 2.
      Patients in Arm 1 will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose RTV
      and RBV and patients in Arm 2 will receive 12 weeks of treatment with TMC435 + TMC647055 +
      low-dose RTV. Panel 4 will consist of 40 chronic HCV GT1a or GT1b infected treatment-naïve
      patients/prior relapsers who will be allocated to 2 arms: each arm will consist of 20
      patients of which at most 8 patients will be infected with HCV GT1b. Patients will be
      randomized in 1:1 ratio between the 2 arms whereby randomization will be stratified by
      genotype. Patients in Arm 1 will receive 12 weeks of treatment with TMC435 + TMC647055 +
      low-dose RTV + GSK2336805. Patients in Arm 2 will receive 12 weeks of treatment with TMC435 +
      TMC647055 + low-dose RTV + GSK2336805. The planned duration of the investigational treatment
      is 12 weeks. Patients in Panels 1, 2, and 3 may receive follow-up treatment with 12 weeks or
      36 weeks of PegIFNα + RBV; follow-up treatment principles will not apply to Panel 4 as based
      on available proof of concept data for such combinations, the need for an additional 12 or
      36-week PegIFN/RBV follow-up therapy is expected to be very low when evaluating a 12-week
      regimen of 3 direct acting antiviral agents for treatment of HCV genotype 1 infections.
      Safety will be monitored throughout the study
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with a sustained virologic response (SVR) 12 Weeks after the actual end of treatment
time frame: Week 24 (Up to 12 weeks after end-of treatment visit)
description: SVR12 is defined as undetectable HCV RNA at the actual end of treatment and HCV RNA less than 25 IU/mL at 12 Weeks after the actual end of treatment.
measure: Number of patients with adverse events
time frame: Up to Week 48 (24 weeks after end of treatment)
description: Number of patients with adverse events, serious adverse events, abnormal changes in safety related laboratory values, abnormal changes in vital signs and physical examination, and abnormal echocardiogram.
measure: Number of patients with a sustained virological response (SVR at 4 and/or 24 Weeks after the actual end of treatment)
time frame: Up to 24 weeks after end of treatment
measure: HCV RNA levels over time
time frame: Up to 24 weeks after end of treatment
measure: Number of patients with undetectable hepatitis C virus (HCV) RNA (less than 25 IU/mL undetectable) and/or HCV RNA levels less than 25 IU/mL at all time points
time frame: Up to 24 weeks after end of treatment
measure: Number of patients with on-treatment virologic failure
time frame: End of treatment (Week 48)
measure: Number of patients with viral relapse
time frame: Up to 24 weeks after end of treatment
measure: Number of patients with presence of HCV variants associated with reduced susceptibility to investigational treatment
time frame: Up to 24 weeks after end of treatment
measure: Maximum plasma analyte concentration of TMC435
time frame: Week 4
measure: Minimum plasma analyte concentration of TMC435
time frame: Week 4
measure: Area under the plasma concentration-time curve of TMC435
time frame: Week 4
measure: Maximum plasma analyte concentration of TMC647055
time frame: Week 4
measure: Minimum plasma analyte concentration of TMC647055
time frame: Week 4
measure: Area under the plasma concentration-time curve of TMC647055
time frame: Week 4
measure: Maximum plasma analyte concentration of ritonavir (RTV)
time frame: Week 4
measure: Minimum plasma analyte concentration of RTV
time frame: Week 4
measure: Area under the plasma concentration-time curve of RTV
time frame: Week 4
measure: Minimum and maximum plasma concentrations of GSK233680k
time frame: Week 4
measure: Area under the plasma concentration-time curve of GSK233680k
time frame: Week 4
arm group label: Panel 1
arm group type: Experimental
description: 10 chronic HCV genotype 1a (GT1a) infected treatment-naive patients/prior relapsers who will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose ritonavir and ribavirin.
arm group label: Panel 2 Arm 1
arm group type: Experimental
description: 10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir and ribavirin.
arm group label: Panel 2 Arm 2
arm group type: Experimental
description: 10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir.
arm group label: Panel 3 - Arm 1
arm group type: Experimental
description: 8 chronic HCV GT1a infected treatment naïve patients/prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir + ribavirin.
arm group label: Panel 3 - Arm 2
arm group type: Experimental
description: 8 chronically HCV GT1b infected treatment naïve patients/prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir.
arm group label: Panel 4 - Arm 1
arm group type: Experimental
description: 20 chronic HCV GT1a or GT1b infected treatment-naive patients/ prior relapsers will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose RTV + GSK2336805 (30 mg once daily)
arm group label: Panel 4 - Arm 2
arm group type: Experimental
description: 20 chronic HCV GT1a or GT1b infected treatment-naive patients/ prior relapsers will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose RTV + GSK2336805 (60 mg once daily)
intervention type: Drug
intervention name: TMC647055
description: Type=exact number, unit=mg, number=150, form=capsule, route=oral. 3 or 4 capsules of 150 mg will be administered once daily.
arm group label: Panel 1
arm group label: Panel 2 Arm 1
arm group label: Panel 2 Arm 2
arm group label: Panel 3 - Arm 1
arm group label: Panel 3 - Arm 2
arm group label: Panel 4 - Arm 1
arm group label: Panel 4 - Arm 2
other name: JNJ-42039556-AMR-G-001
intervention type: Drug
intervention name: TMC435
description: Type=exact number, unit=mg, number=75, form=capsule, route=oral. 1 capsule of 75 mg will be administered once daily.
arm group label: Panel 1
arm group label: Panel 2 Arm 1
arm group label: Panel 2 Arm 2
arm group label: Panel 3 - Arm 1
arm group label: Panel 3 - Arm 2
arm group label: Panel 4 - Arm 1
arm group label: Panel 4 - Arm 2
intervention type: Drug
intervention name: Ritonavir
description: Type=exact number, unit=mg, number=30 or 50, form=tablet or solution, route=oral. 0.375 mL or 0.625 ml (80 mg/mL) solution will be administered once daily.
arm group label: Panel 1
arm group label: Panel 2 Arm 1
arm group label: Panel 2 Arm 2
arm group label: Panel 3 - Arm 1
arm group label: Panel 3 - Arm 2
arm group label: Panel 4 - Arm 1
arm group label: Panel 4 - Arm 2
intervention type: Drug
intervention name: Ribavirin
description: Type=exact number, unit=mg, number=200, form=tablet, route=oral. 5 to 6 (1000 or 1200 mg) tablets will be administered once daily, divided in 2 daily doses. Patients meeting the Follow-UP (FU) treatment criteria specified in the protocol will receive treatment 5 or 6 (depending on bodyweight) tablets of ribavirin (equivalent to 200 mg/tablet) per day, divided in 2 daily doses for an additional 12 or 36 weeks.
arm group label: Panel 1
arm group label: Panel 2 Arm 1
arm group label: Panel 2 Arm 2
arm group label: Panel 3 - Arm 1
intervention type: Drug
intervention name: Pegylated interferon alpha-2a (PegIFN)
description: Type=exact number, unit=mcg, number=180, form=solution, route=subcutaneous injection. PegIFN 0.5 mL prefilled syringe equivalent to 180 mcg will be administered as a subcutaneous (under the skin) injection as follow-up (FU) treatment for 12 or 36 weeks based on follow-up treatment principles as described in the protocol. Patients meeting the Follow-UP (FU) treatment criteria specified in the protocol will receive treatment with Pegylated interferon alpha-2a (PegIFN) 0.5 mL prefilled syringe equivalent to 180 mcg administered as a subcutaneous (under the skin) injection for an additional 12 or 36 weeks.
arm group label: Panel 1
arm group label: Panel 2 Arm 1
arm group label: Panel 2 Arm 2
arm group label: Panel 3 - Arm 1
arm group label: Panel 3 - Arm 2
intervention type: Drug
intervention name: GSK2336805
description: Type=exact number, unit=mg, number=30 or 60, form=tablet, route=subcutaneous injection. GSK2336805 one or two 30 mg tablet(s) taken orally (by mouth) once daily for 12 weeks.
arm group label: Panel 4 - Arm 1
arm group label: Panel 4 - Arm 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Janssen R&D Ireland Clinical Trial
role: Study Director
affiliation: Janssen R&D Ireland
facility: 
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country: Belgium
country: Germany
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis C, Chronic
mesh term: Hepatitis
mesh term: Hepatitis, Chronic
mesh term: Interferons
mesh term: Ritonavir
mesh term: Ribavirin
mesh term: Interferon-alpha
mesh term: Interferon alpha-2
mesh term: Peginterferon alfa-2a
mesh term: Simeprevir