<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/NCT03037151</url>
  </required_header>
  <id_info>
    <org_study_id>HIV-NAT 245</org_study_id>
    <nct_id>NCT03037151</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Grazoprevir and Elbasvir for GT1ang GT6 With and Without HIV</brief_title>
  <official_title>Safety and Fibrosis Improvement of Grazoprevir and Elbasvir for HCV GT1 and GT6 With or Without HIV</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The HIV Netherlands Australia Thailand Research Collaboration</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chulalongkorn University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The HIV Netherlands Australia Thailand Research Collaboration</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the safety and efficacy of combination treatment with grazoprevir +&#xD;
      elbasvir for compensated cirrhotic participants with chronic genotype 1 (GT1) and genotype 6&#xD;
      (GT6) hepatitis C virus (HCV) infection with or without human immunodeficiency virus (HIV)&#xD;
      infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Total 100 patients with compensated cirrhosis, chronically infected with HCV GT1 or GT6 with&#xD;
      or without HIV infection will be included. Patients with HCV GT1 and GT6 will be enrolled on&#xD;
      a 1:1 basis (approximately 50 patients with GT1 and 50 patients with GT6). Treatment-naïve&#xD;
      patients will be treated with the combination of grazoprevir plus elbasvir for 12 weeks.&#xD;
      Treatment-experienced patients, including null responders, partial responders or&#xD;
      post-treatment relapsers, will be assigned to treat with the combination plus weight-based&#xD;
      RBV for 16 weeks. The dosages of study drugs are 100 mg of grazoprevir once daily and 50 mg&#xD;
      of elbasvir once daily. All patients will follow up to assess SVR (defined by HCV RNA level&#xD;
      &lt;12 IU/mL) at week12 and week 24 after treatment (SVR12 and SVR24, respectively).&#xD;
      Additionally, participants will be evaluated the longitudinal changes in LS values by TE up&#xD;
      to 240 weeks (5 years) after treatment&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">August 1, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <phase>Phase 4</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>Rate of SVR12</measure>
    <time_frame>12 weeks post-treatment</time_frame>
    <description>To evaluate the rate of sustained virological response (SVR) at 12 weeks after the end of treatment (SVR12) in compensated cirrhotic participants with GT1 and GT6 HCV infection with or without HIV infection treated with the combination of grazoprevir and elbasvir</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of SVR24</measure>
    <time_frame>24 weeks post-treatment</time_frame>
    <description>To evaluate the rate of sustained virological response (SVR) at 24 weeks after the end of treatment (SVR24)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Decline of liver stiffness</measure>
    <time_frame>5 years post-treatment</time_frame>
    <description>To evaluate the percentage of participants achieving a significant decline in liver stiffness (LS) values (defined as a ≥30% decrease from baseline) up to 240 weeks (5 years) after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in liver stiffness</measure>
    <time_frame>5 years</time_frame>
    <description>To compare the longitudinal changes in LS values over time between participants and untreated historical controls</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Compensated Cirrhosis</condition>
  <arm_group>
    <arm_group_label>HCV mono-infection Treatment naives</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HCV treatment-naïve patients will be treated with the combination of grazoprevir plus elbasvir for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HCV mono-infection Treatment experienced</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HCV treatment-experienced patients, including null responders, partial responders or post-treatment relapsers, will be assigned to treat with the combination plus weight-based RBV for 16 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HCV/HIV co-infection Treatment naives</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HCV/HIV coinfected, treatment-naïve patients will be treated with the combination of grazoprevir plus elbasvir for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HCV/HIV co-infection Treatment experienced</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HCV/HIV co-infected treatment-experienced patients, including null responders, partial responders or post-treatment relapsers, will be assigned to treat with the combination plus weight-based RBV for 16 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Grazaoprevir/Elbasavir</intervention_name>
    <description>treatment naive</description>
    <arm_group_label>HCV mono-infection Treatment naives</arm_group_label>
    <arm_group_label>HCV/HIV co-infection Treatment naives</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Grazaoprevir/Elbasavir/RBV</intervention_name>
    <description>treatment experienced</description>
    <arm_group_label>HCV mono-infection Treatment experienced</arm_group_label>
    <arm_group_label>HCV/HIV co-infection Treatment experienced</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men and women aged 18 years or older&#xD;
&#xD;
          2. Documented chronic HCV GT1 or GT6 (positive for anti-HCV antibody and HCV RNA at least&#xD;
             6 months prior to screening)&#xD;
&#xD;
          3. HCV RNA of at least 10,000 IU/ml&#xD;
&#xD;
          4. Cirrhosis defined by: liver biopsy showing cirrhosis METAVIR F4; or TE showing&#xD;
             cirrhosis with a result of &gt;13.0 kPa&#xD;
&#xD;
          5. Treatment-naïve individuals for chronic HCV infection&#xD;
&#xD;
          6. Treatment-experienced individuals (Previous treatment failure with PEG-IFN plus RBV)&#xD;
             for chronic HCV infection&#xD;
&#xD;
          7. HIV-infected participants enrolled in this study must meet following criteria:&#xD;
&#xD;
             7.1 Documented HIV infection 7.2 Naïve to treatment with any antiretroviral therapy&#xD;
             (ART) or on HIV ART for at least 8 weeks prior to study entry using a dual nucleoside&#xD;
             reverse transcriptase inhibitor (NRTI) backbone of tenofovir or abacavir and either&#xD;
             emtricitabine or lamivudine plus raltegravir (or dolutegravir or rilpivirine) 7.3 CD4+&#xD;
             T-cell count &gt;200 cells/mm3 if on ART or &gt;500 cell/mm3 if ART treatment naïve 7.4&#xD;
             Undetectable plasma HIV-RNA at least 8 weeks prior to screening if on ART or &lt;50,000&#xD;
             copies/mL if ART treatment naïve&#xD;
&#xD;
          8. Agree to use two acceptable methods of birth control from at least 2 weeks prior to&#xD;
             Day 1 and continue until at least 6 months after last dose of study drug, or longer if&#xD;
             dictated by local regulations (for female subject who is of childbearing potential or&#xD;
             male subject with female sexual partner who is of childbearing potential).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Evidence of decompensated liver disease (Child-Pugh Class B or C or Child-Pugh score&#xD;
             &gt;6, platelets less than 75 × 10³/μL, serum albumin &lt; 3·0 g/dL, presence of or history&#xD;
             of ascites, gastric or variceal bleeding, hepatic encephalopathy or other signs or&#xD;
             symptoms of advanced liver disease)&#xD;
&#xD;
          2. Co-infected with hepatitis B virus&#xD;
&#xD;
          3. Has cirrhosis and liver imaging within 6 months showing evidence of HCC or is under&#xD;
             evaluation for HCC&#xD;
&#xD;
          4. Pregnant or breast-feeding from day 1 or anytime during treatment, and 14 days after&#xD;
             the last dose of study medication&#xD;
&#xD;
          5. Any medical condition requiring or likely to require chronic systemic administration&#xD;
             of corticosteroids or other immunosuppressant drugs during the course of the study&#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>Anchalee Avihingsanon, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>HIV-NAT, Thai Red Cross - AIDS Research Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pisit Tangkijvanich, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chulalongkorn University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Faculty of Medicine, Chulalongkorn University</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HIV-NAT, Thai Red Cross AIDS Research Centre</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <link>
    <url>http://www.hivnat.org</url>
    <description>Related Info</description>
  </link>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>January 27, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>February 11, 2020</last_update_submitted>
  <last_update_submitted_qc>February 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Safety</keyword>
  <keyword>Efficacy</keyword>
  <keyword>grazoprevir</keyword>
  <keyword>elbasvir</keyword>
  <keyword>compensated cirrhosis</keyword>
  <keyword>genotype 1 (GT1)</keyword>
  <keyword>genotype 6 (GT6)</keyword>
  <keyword>hepatitis virus C (HCV)</keyword>
  <keyword>human immunodeficiency virus (HIV)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>only when needed as per the auditing/monitoring processes and requirement</ipd_description>
  </patient_data>
  <!-- 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/NCT03037151
org study id: HIV-NAT 245
nct id: NCT03037151
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will evaluate the safety and efficacy of combination treatment with grazoprevir +
      elbasvir for compensated cirrhotic participants with chronic genotype 1 (GT1) and genotype 6
      (GT6) hepatitis C virus (HCV) infection with or without human immunodeficiency virus (HIV)
      infection.
Total 100 patients with compensated cirrhosis, chronically infected with HCV GT1 or GT6 with
      or without HIV infection will be included. Patients with HCV GT1 and GT6 will be enrolled on
      a 1:1 basis (approximately 50 patients with GT1 and 50 patients with GT6). Treatment-naïve
      patients will be treated with the combination of grazoprevir plus elbasvir for 12 weeks.
      Treatment-experienced patients, including null responders, partial responders or
      post-treatment relapsers, will be assigned to treat with the combination plus weight-based
      RBV for 16 weeks. The dosages of study drugs are 100 mg of grazoprevir once daily and 50 mg
      of elbasvir once daily. All patients will follow up to assess SVR (defined by HCV RNA level
      <12 IU/mL) at week12 and week 24 after treatment (SVR12 and SVR24, respectively).
      Additionally, participants will be evaluated the longitudinal changes in LS values by TE up
      to 240 weeks (5 years) after treatment
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of SVR12
time frame: 12 weeks post-treatment
description: To evaluate the rate of sustained virological response (SVR) at 12 weeks after the end of treatment (SVR12) in compensated cirrhotic participants with GT1 and GT6 HCV infection with or without HIV infection treated with the combination of grazoprevir and elbasvir
measure: Rate of SVR24
time frame: 24 weeks post-treatment
description: To evaluate the rate of sustained virological response (SVR) at 24 weeks after the end of treatment (SVR24)
measure: Decline of liver stiffness
time frame: 5 years post-treatment
description: To evaluate the percentage of participants achieving a significant decline in liver stiffness (LS) values (defined as a ≥30% decrease from baseline) up to 240 weeks (5 years) after treatment
measure: changes in liver stiffness
time frame: 5 years
description: To compare the longitudinal changes in LS values over time between participants and untreated historical controls
arm group label: HCV mono-infection Treatment naives
arm group type: Experimental
description: HCV treatment-naïve patients will be treated with the combination of grazoprevir plus elbasvir for 12 weeks.
arm group label: HCV mono-infection Treatment experienced
arm group type: Experimental
description: HCV treatment-experienced patients, including null responders, partial responders or post-treatment relapsers, will be assigned to treat with the combination plus weight-based RBV for 16 weeks.
arm group label: HCV/HIV co-infection Treatment naives
arm group type: Experimental
description: HCV/HIV coinfected, treatment-naïve patients will be treated with the combination of grazoprevir plus elbasvir for 12 weeks.
arm group label: HCV/HIV co-infection Treatment experienced
arm group type: Experimental
description: HCV/HIV co-infected treatment-experienced patients, including null responders, partial responders or post-treatment relapsers, will be assigned to treat with the combination plus weight-based RBV for 16 weeks.
intervention type: Drug
intervention name: Grazaoprevir/Elbasavir
description: treatment naive
arm group label: HCV mono-infection Treatment naives
arm group label: HCV/HIV co-infection Treatment naives
intervention type: Drug
intervention name: Grazaoprevir/Elbasavir/RBV
description: treatment experienced
arm group label: HCV mono-infection Treatment experienced
arm group label: HCV/HIV co-infection Treatment experienced
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anchalee Avihingsanon, MD, PhD
role: Principal Investigator
affiliation: HIV-NAT, Thai Red Cross - AIDS Research Centre
last name: Pisit Tangkijvanich, MD
role: Principal Investigator
affiliation: Chulalongkorn University
facility: 
facility: 
country: Thailand
url: http://www.hivnat.org
description: Related Info
responsible party type: Sponsor
mesh term: Fibrosis
sharing ipd: No
ipd description: only when needed as per the auditing/monitoring processes and requirement