<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/NCT02973503</url>
  </required_header>
  <id_info>
    <org_study_id>CHU-0285</org_study_id>
    <secondary_id>2016-001363-37</secondary_id>
    <nct_id>NCT02973503</nct_id>
  </id_info>
  <brief_title>Study to Investigate the Efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, With Non-severe Fibrosis</brief_title>
  <acronym>STREAGER</acronym>
  <official_title>A Phase 3, Global, Multicenter, Open-Label Study to Investigate the Efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, With Non-severe Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Clermont-Ferrand</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Clermont-Ferrand</source>
  <brief_summary>
    <textblock>
      A Phase 3, Global, Multicenter, Open-Label Study to Investigate the Efficacy of&#xD;
      Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected&#xD;
      Patients, with non-severe fibrosis&#xD;
&#xD;
      The primary objectives of this study are as follows:&#xD;
&#xD;
        -  To evaluate the efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in&#xD;
           Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by&#xD;
           the proportion of subjects with sustained viral response 12 weeks after cessation of&#xD;
           treatment (SVR 12).&#xD;
&#xD;
        -  To evaluate the safety and tolerability of EBV/GZR treatment&#xD;
&#xD;
      The secondary objectives of this study are as follows:&#xD;
&#xD;
        -  To determine the proportion of subjects who attain SVR at 4 and 24 weeks after cessation&#xD;
           of treatment (SVR4 and SVR24)&#xD;
&#xD;
        -  To evaluate the proportion of subjects with virologic failure&#xD;
&#xD;
        -  To evaluate the kinetics of circulating HCV RNA during treatment and after cessation of&#xD;
           treatment.&#xD;
&#xD;
        -  To evaluate the emergence of viral resistance to EBV/GZR during treatment and after&#xD;
           cessation of treatment&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      One hundred twenty treatment-naïve subjects with chronic HCV GT1b infection without cirrhosis&#xD;
      will be enrolled.&#xD;
&#xD;
      There will be one treatment group with EBV/GZR (50/100 mg) once daily without regards to food&#xD;
      for 8 weeks.&#xD;
&#xD;
      EBV/GZR is manufactured as a 50/100 mg tablet for oral administration. Subjects will take 1&#xD;
      tablet daily.&#xD;
&#xD;
      Screening assessments will be completed within 28 days of the Day 1 visit. The screening&#xD;
      window can be extended to 42 days for subjects requiring a liver biopsy, or extenuating&#xD;
      circumstances.&#xD;
&#xD;
      All subjects will complete the following study visits: Screening, Day 1, and on-treatment&#xD;
      visits at the end of week 2, week 4 and week 8.&#xD;
&#xD;
      Post-treatment visits will occur at Weeks 4, 12, and 24 after last dose of study drug. All&#xD;
      subjects will complete the posttreatment Week 4 and 12 visits. Subjects who achieve SVR12&#xD;
      (HCV RNA &lt; LLOQ at posttreatment Week12) will complete the posttreatment Week 24 visit.&#xD;
&#xD;
      Screening assessments will include physical examination, medical history, height, weight,&#xD;
      vital signs, adverse events related to screening procedures, concomitant medications, safety&#xD;
      laboratory tests (including hematology, chemistry, and coagulation), HCV RNA, serology (HCV,&#xD;
      HBV), serology and/or antigen testing for HIV, HCV genotyping, hemoglobin A1c (HbA1c),&#xD;
      assessment of the absence of cirrhosis or severe fibrosis (including Fibrotest® and&#xD;
      Fibroscan®), serum β-human chorionic gonadotropin (β-hCG) (females of child-bearing potential&#xD;
      only), urinalysis.&#xD;
&#xD;
      On-treatment assessments include adverse events (AEs), concomitant medications, study&#xD;
      medication dispensation and pill count, physical examination, weight, vital signs, safety&#xD;
      laboratory tests, HCV RNA, and urine pregnancy tests (females of child bearing potential&#xD;
      only).&#xD;
&#xD;
      Post-treatment assessments include AEs, concomitant medications, vital signs, safety&#xD;
      laboratory tests (including hematology, chemistry, and coagulation), HCV RNA, and urine&#xD;
      pregnancy tests (females of child-bearing potential only).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 11, 2017</start_date>
  <completion_date type="Actual">April 2019</completion_date>
  <primary_completion_date type="Actual">November 10, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluation of the Efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve as Measured by the Proportion of Subjects With Sustained Viral Response 12 Weeks After Cessation of Treatment (SVR 12).</measure>
    <time_frame>at 12 weeks post-treatment</time_frame>
    <description>Blood samples for HCV RNA determination were collected 12 weeks after cessation of treatment and analysed by local laboratories tests</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Asthenia Reported</measure>
    <time_frame>Between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks</time_frame>
    <description>Asthenia was defined by abnormal physical weakness or lack of energy. Asthenia was monitored throughout the study and up to 24 weeks after planned end of treatment. An investigator who is a qualified physician evaluated all adverse events, causality and severity. Only grade 1 or 2 were reported. No grade 3. Grade was evaluated with table 9 of protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Headache Reported</measure>
    <time_frame>between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks</time_frame>
    <description>Headache is defined by pain felt in the cranial box. Headache was monitored throughout the study and up to 24 weeks after planned end of treatment. An investigator who is a qualified physician evaluated all adverse events, causality and severity. Only grade 1 or 2 were reported. No grade 3. grade was evaluated with table 9 of protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Digestive Disorders Reported</measure>
    <time_frame>Between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks</time_frame>
    <description>Digestive disorders is defined by an acceleration, a slowing down or a disturbance of the intestinal transit with or without pain. Digestive disorders were monitored throughout the study and up to 24 weeks after planned end of treatment. An investigator who is a qualified physician evaluated digestive disorders causality and severity. Only grade 1 or 2 were reported. No grade 3. Grade was evaluated with table 9 of protocol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects Who Attain SVR at 4 Weeks After Cessation of Treatment (SVR4)</measure>
    <time_frame>at 4 weeks after cessation of treatment</time_frame>
    <description>blood samples were collected at 4 weeks after cessation of treatment and HCV RNA was measured using local laboratories tests</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects Who Attain SVR 24 Weeks After Cessation of Treatment (SVR 24)</measure>
    <time_frame>at 24 weeks after cessation of treatment</time_frame>
    <description>blood samples were collected at 24 weeks after cessation of treatment and HCV RNA was measured using local laboratories tests</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Virologic Failure</measure>
    <time_frame>at 12 weeks after cessation of treatment</time_frame>
    <description>patient with HCV RNA &gt; low limit of quantification in two different consecutive blood samples were considered as relapser</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the Emergence of Viral Resistance to EBV/GZR at 24 Weeks After Cessation of Treatment</measure>
    <time_frame>at 24 weeks after end of treatment</time_frame>
    <description>Patients with HCV RNA&gt; low limit of quantification in two consecutive blood samples were considered as relapsers.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">117</enrollment>
  <condition>Chronic HCV Infection</condition>
  <arm_group>
    <arm_group_label>Elbasvir/Grazoprevir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>evaluate the efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Elbasvir/Grazoprevir Fixed Dose Combination</intervention_name>
    <description>Evaluate the efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).</description>
    <arm_group_label>Elbasvir/Grazoprevir</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing and able to provide written informed consent&#xD;
&#xD;
          -  Male or female, age ≥ 18 years&#xD;
&#xD;
          -  Body Mass Index (BMI) ≥ 18 kg/m2&#xD;
&#xD;
          -  HCV RNA ≥ 100 000 IU/mL at Screening&#xD;
&#xD;
          -  Chronic HCV infection (≥ 6 months) documented by prior medical history or liver&#xD;
             biopsy, only genotype 1b virus. (Positive for anti HCV antibody, HCV RNA, or an HCV&#xD;
             genotype)&#xD;
&#xD;
          -  Treatment-naïve with no prior exposure to any IFN, RBV, or approved or experimental&#xD;
             HCV-specific DAA&#xD;
&#xD;
          -  Non severe fibrosis (F&lt;2) according to combination of this two tests :&#xD;
&#xD;
        Fibroscan lower than 9.5kPa and Fibrotest lower than 0.59&#xD;
&#xD;
          -  Females of childbearing potential (as defined in protocol Appendix 4) must have a&#xD;
             negative serum pregnancy test at screening and a negative urine pregnancy test on Day&#xD;
             1 prior to enrollment&#xD;
&#xD;
          -  Male subjects and female subjects of childbearing potential who engage in heterosexual&#xD;
             intercourse must agree to use 2 effective method(s) of contraception from at least two&#xD;
             weeks prior to Day 1 through 14 days after the last dose of study drugs.&#xD;
&#xD;
               -  If acceptable by local regulatory agencies, methods of birth control allowed in&#xD;
                  the study are: intrauterine device (IUD), diaphragm with spermicide, hormonal&#xD;
                  contraceptives (e.g., birth control pills, transdermal patch, or injectables),&#xD;
                  contraceptive sponge, female condom, male condom with spermicide or vasectomy.&#xD;
&#xD;
               -  Note: Periodic abstinence (e.g., abstinence only on certain calendar days,&#xD;
                  abstinence only during ovulation period, use of symptothermal methods, use of&#xD;
                  post-ovulation methods and withdrawal) are not acceptable methods of&#xD;
                  contraception.&#xD;
&#xD;
          -  A female subject who is not of reproductive potential is eligible without requiring&#xD;
             the use of contraception. A female subjects who is not of reproductive potentials is&#xD;
             defined as one who has either 1) reached natural menopause (defined as 12 months with&#xD;
             no menses without an alternative medical cause), 2) 6 weeks post surgical bilateral&#xD;
             oophorectomy with or without hysterectomy, or 3) bilateral tubal ligation.&#xD;
&#xD;
          -  A male subject who is not of reproductive potential is eligible without requiring the&#xD;
             use of contraception. A male subject who is not of reproductive potential is defined&#xD;
             as: one who has undergone a successful vasectomy. A successful vasectomy is defined&#xD;
             as: (1) microscopic documentation of azoospermia, or (2) a vasectomy more than 2 years&#xD;
             ago with no resultant pregnancy despite sexual activity post vasectomy.&#xD;
&#xD;
          -  Lactating females must agree to discontinue nursing before starting study drug&#xD;
&#xD;
          -  Subject must be of generally good health, with the exception of chronic HCV infection,&#xD;
             as determined by the Investigator&#xD;
&#xD;
          -  Subject must be able to comply with the dosing instructions for study drug&#xD;
             administration and able to complete the study schedule of assessments&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is under the age of legal consent, is mentally or legally incapacitated, has&#xD;
             significant emotional problems at the time of pre-study screening visit or expected&#xD;
             during the conduct of the study or has a history of a clinically significant&#xD;
             psychiatric disorder which, in the opinion of the investigator, would interfere with&#xD;
             the study procedures.&#xD;
&#xD;
          -  Current or prior history of any of the following:&#xD;
&#xD;
               -  Clinically significant illness (other than HCV) or any other major medical&#xD;
                  disorder that may interfere with subject treatment, assessment or compliance with&#xD;
                  the protocol; subjects currently under evaluation for a potentially clinically&#xD;
                  significant illness (other than HCV) are also excluded&#xD;
&#xD;
               -  Gastrointestinal disorder or post-operative condition that could interfere with&#xD;
                  the absorption of the study drug&#xD;
&#xD;
               -  Difficulty with blood collection and/or poor venous access for the purposes of&#xD;
                  phlebotomy&#xD;
&#xD;
               -  History of decompensation (e.g., clinical ascites, encephalopathy, and/or&#xD;
                  variceal hemorrhage)&#xD;
&#xD;
               -  Solid organ transplantation (including hematopoietic stem cell transplants) other&#xD;
                  than kidney, cornea and hair.&#xD;
&#xD;
               -  Significant cardiac disease&#xD;
&#xD;
               -  Unstable psychiatric condition including hospitalization, suicidal attempt,&#xD;
                  and/or a period of disability as a result of their psychiatric illness within 2&#xD;
                  years prior to Screening&#xD;
&#xD;
               -  Malignancy within the 5 years prior to Screening, with the exception of specific&#xD;
                  cancers that have been cured by surgical resection (e.g., basal cell skin cancer,&#xD;
                  etc.). Subjects under evaluation for possible malignancy are not eligible&#xD;
&#xD;
               -  Significant drug allergy (e.g., hepatotoxicity)&#xD;
&#xD;
          -  Subject has the following laboratory parameters at Screening:&#xD;
&#xD;
               -  ALT &gt; 10 x the upper limit of normal (ULN)&#xD;
&#xD;
               -  AST &gt; 10 x ULN&#xD;
&#xD;
               -  Direct bilirubin &gt; 1.5 x ULN&#xD;
&#xD;
               -  Platelets &lt; 75,000/μL&#xD;
&#xD;
               -  HbA1c &gt; 8.5%&#xD;
&#xD;
               -  Creatinine clearance &lt; 50 mL/min as calculated by the Cockcroft-Gault equation&#xD;
&#xD;
               -  Hemoglobin &lt; 10 g/dL&#xD;
&#xD;
               -  Albumin &lt; 3 g/dL&#xD;
&#xD;
               -  INR &gt; 1.5 x ULN unless subject has known hemophilia or is stable on an&#xD;
                  anticoagulant regime affecting INR&#xD;
&#xD;
          -  Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease,&#xD;
             alfa-1 antitrypsin deficiency, cholangitis)&#xD;
&#xD;
          -  Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Clinically-relevant alcohol or drug abuse within 12 months of Screening.&#xD;
&#xD;
               -  Alcohol, intravenous drugs, inhalational (not including marijuana), psychotropic,&#xD;
                  narcotics, cocaine use, prescription or over-the-counter drugs: within 1 year of&#xD;
                  the screening visit, or if shorter, is judged by investigator to be capable of&#xD;
                  complying with study procedures&#xD;
&#xD;
               -  receiving opiate agonist substitution therapy within 1 year of screening visit,&#xD;
                  or if shorter, is judged by investigator to be capable of complying with study&#xD;
                  procedures&#xD;
&#xD;
               -  history of marijuana use if deemed excessive by a physician investigator or&#xD;
                  interferes with the subject's daily function. If subject's marijuana use is not&#xD;
                  deemed excessive and does not interfere with daily function, subject must agree&#xD;
                  to discontinue any current use of recreational marijuana prior to entry into&#xD;
                  trial and throughout the trial period&#xD;
&#xD;
                    -  A positive drug screen will exclude subjects unless it can be explained by a&#xD;
                       prescribed medication; the diagnosis and prescription must be approved by&#xD;
                       the investigator&#xD;
&#xD;
          -  Use of any prohibited concomitant medication listed in Section 5.5 of this protocol&#xD;
             within 2 weeks prior to day 1.&#xD;
&#xD;
          -  Known hypersensitivity to the study drug, the metabolites, or formulation excipient&#xD;
&#xD;
          -  is currently participating or has participated in a study with an investigational&#xD;
             compound within 30 days of signing informed consent and is not willing to refrain from&#xD;
             participating in another study. Collection of additional blood, urine, or tissue&#xD;
             samples or additional data, beyond that specified in this protocol, is prohibited&#xD;
             (other than that related to subject's medical care).&#xD;
&#xD;
          -  (female) is pregnant, lactating, expecting to conceive or donate eggs, or is of&#xD;
             childbearing potential and unwilling to commit to two methods of birth control&#xD;
             throughout treatment and after the completion of all treatment (see Inclusion&#xD;
             Criteria); or male subject is planning to impregnate or provide sperm donation or has&#xD;
             a female sexual partner of childbearing potential and is unwilling to commit to using&#xD;
             a two methods of birth control throughout treatment and after the completion of all&#xD;
             treatment (see Inclusion Criteria).&#xD;
&#xD;
          -  had a life-threatening SAE during the screening period. 2. is a member or a family&#xD;
             member of the investigational study staff or sponsor staff directly involved with this&#xD;
             study.&#xD;
&#xD;
          -  has evidence or history of chronic hepatitis not caused by HCV, including but not&#xD;
             limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune&#xD;
             hepatitis.&#xD;
&#xD;
               -  NOTE: Subjects with history of acute non-HCV-related hepatitis, which resolved &gt;&#xD;
                  6 months before study entry, may be enrolled.&#xD;
&#xD;
          -  For subjects diagnosed with diabetes mellitus, documented HbA1c &gt;8.5% (to exclude&#xD;
             uncontrolled diabetes).&#xD;
&#xD;
          -  Has any of the following conditions:.&#xD;
&#xD;
               -  Subject with a history of gastric surgery (e.g., stapling, bypass) or subject&#xD;
                  with a history of malabsorption disorders (e.g., celiac sprue disease).&#xD;
&#xD;
               -  Any medical condition requiring, or likely to require, chronic systemic&#xD;
                  administration of corticosteroids during the course of the trial.&#xD;
&#xD;
          -  Has exclusionary laboratory values as listed below (see Table 5 for unit conversions&#xD;
             of some laboratory values specified below):&#xD;
&#xD;
               -  Note: If any of the laboratory exclusion criteria below are met, the site may&#xD;
                  have the abnormal value retested one time.&#xD;
&#xD;
        Table 5: Exclusionary laboratory values:&#xD;
&#xD;
          -  Laboratory Assessment&#xD;
&#xD;
          -  hemoglobin &lt; LLN (lower limit of normal) of laboratory reference range&#xD;
&#xD;
          -  neutrophils &lt;1.5 x 103/μL (&lt;1.2 x 103/μL for Blacks)&#xD;
&#xD;
          -  platelets &lt;75 x 103/μL&#xD;
&#xD;
          -  direct bilirubin &gt;1.5 x ULN&#xD;
&#xD;
          -  Total Bilirubin &gt;1.6 mg/dL unless history of Gilbert's disease. (If Gilbert's disease&#xD;
             is the proposed etiology, this must be documented in the subject's chart)&#xD;
&#xD;
          -  Serum Albumin &lt; 3.0 g/dL (lower limit of normal) of laboratory reference range&#xD;
&#xD;
          -  creatinine clearance &lt;50 mL/min&#xD;
&#xD;
          -  INR &gt;1.5&#xD;
&#xD;
          -  ALT &gt;350&#xD;
&#xD;
          -  AST &gt;350&#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>Armand ABERGEL</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Clermont-Ferrand</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Isabelle FOUCHART-HUBERT</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Angers</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vincent DI MARTINO</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Hospitalier Universitaire de Besancon</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Véronique LOUSTAUD RATTI</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU LIMOGES</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jérôme GOURNAY</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Nantes</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Tarik ASSELAH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpital Beaujon</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Didier SAMUEL</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpital Paul Brousse</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dominique LARREY</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Montpellier</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sophie METIVIER</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Toulouse Hopital Purpan</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Christophe HEZODE</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Henri Mondor</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Albert TRAN</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Nice hopital Archet II</affiliation>
  </overall_official>
  <overall_official>
    <last_name>François BAILLY</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospice civils de Lyon, hopital de la croix Rousse</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stanislas POL</last_name>
    <role>Principal Investigator</role>
    <affiliation>AP-HP Hopital Cochin</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Valérie CANVA</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU de Lille</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU Clermont-Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>October 14, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 25, 2016</study_first_posted>
  <results_first_submitted>June 30, 2020</results_first_submitted>
  <results_first_submitted_qc>August 20, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">September 7, 2020</results_first_posted>
  <last_update_submitted>September 9, 2020</last_update_submitted>
  <last_update_submitted_qc>September 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatitis C</keyword>
  <keyword>Genotype 1B</keyword>
  <keyword>Non Severe Fibrosis</keyword>
  <keyword>Treatment Naïve</keyword>
  <keyword>8 Weeks of Treatment</keyword>
  <keyword>Elbasvir/Grazoprevir Combination</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Grazoprevir</mesh_term>
    <mesh_term>Elbasvir-grazoprevir drug combination</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 8, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/03/NCT02973503/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/03/NCT02973503/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Elbasvir/Grazoprevir</title>
          <description>Elbasvir/Grazoprevir Fixed Dose Combination: Evaluate the efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="117"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="117"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>5 PATIENTS WERE EXCLUDED DUE TO GENOTYPE NON 1B</population>
      <group_list>
        <group group_id="B1">
          <title>Elbasvir/Grazoprevir</title>
          <description>Elbasvir/Grazoprevir Fixed Dose Combination: Evaluate the efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="112"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="86"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>YEARS</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54" spread="13"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="77"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>France</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="112"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Evaluation of the Efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve as Measured by the Proportion of Subjects With Sustained Viral Response 12 Weeks After Cessation of Treatment (SVR 12).</title>
        <description>Blood samples for HCV RNA determination were collected 12 weeks after cessation of treatment and analysed by local laboratories tests</description>
        <time_frame>at 12 weeks post-treatment</time_frame>
        <population>117 were enrolled. Five patients were excluded from the analysis population because they were non genotype 1b. 112 patients were analysed in modified intention to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Elbasvir/Grazoprevir</title>
            <description>One group, open label study</description>
          </group>
        </group_list>
        <measure>
          <title>Evaluation of the Efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve as Measured by the Proportion of Subjects With Sustained Viral Response 12 Weeks After Cessation of Treatment (SVR 12).</title>
          <description>Blood samples for HCV RNA determination were collected 12 weeks after cessation of treatment and analysed by local laboratories tests</description>
          <population>117 were enrolled. Five patients were excluded from the analysis population because they were non genotype 1b. 112 patients were analysed in modified intention to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="109"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Asthenia Reported</title>
        <description>Asthenia was defined by abnormal physical weakness or lack of energy. Asthenia was monitored throughout the study and up to 24 weeks after planned end of treatment. An investigator who is a qualified physician evaluated all adverse events, causality and severity. Only grade 1 or 2 were reported. No grade 3. Grade was evaluated with table 9 of protocol.</description>
        <time_frame>Between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks</time_frame>
        <population>117 patients were included and 5 patients were excluded from the analysis because of non genotype 1b. 112 patients were analysed in modified intention to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Patients Treated With Elbasvir / Grazoprevir</title>
            <description>All patients were treated by Elbasvir / Grazoprevir. Asthenia is one of the most important adverse event reported</description>
          </group>
        </group_list>
        <measure>
          <title>Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Asthenia Reported</title>
          <description>Asthenia was defined by abnormal physical weakness or lack of energy. Asthenia was monitored throughout the study and up to 24 weeks after planned end of treatment. An investigator who is a qualified physician evaluated all adverse events, causality and severity. Only grade 1 or 2 were reported. No grade 3. Grade was evaluated with table 9 of protocol.</description>
          <population>117 patients were included and 5 patients were excluded from the analysis because of non genotype 1b. 112 patients were analysed in modified intention to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Headache Reported</title>
        <description>Headache is defined by pain felt in the cranial box. Headache was monitored throughout the study and up to 24 weeks after planned end of treatment. An investigator who is a qualified physician evaluated all adverse events, causality and severity. Only grade 1 or 2 were reported. No grade 3. grade was evaluated with table 9 of protocol.</description>
        <time_frame>between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks</time_frame>
        <population>117 patients were included and 5 patients were excluded from the analysis because of non genotype 1b. 112 patients were analysed in modified intention to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Patients Treated With Elbasvir/Grazoprevir</title>
            <description>All patients were treated by Elbasvir / Grazoprevir. Headach is one of the most important adverse event reported</description>
          </group>
        </group_list>
        <measure>
          <title>Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Headache Reported</title>
          <description>Headache is defined by pain felt in the cranial box. Headache was monitored throughout the study and up to 24 weeks after planned end of treatment. An investigator who is a qualified physician evaluated all adverse events, causality and severity. Only grade 1 or 2 were reported. No grade 3. grade was evaluated with table 9 of protocol.</description>
          <population>117 patients were included and 5 patients were excluded from the analysis because of non genotype 1b. 112 patients were analysed in modified intention to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Digestive Disorders Reported</title>
        <description>Digestive disorders is defined by an acceleration, a slowing down or a disturbance of the intestinal transit with or without pain. Digestive disorders were monitored throughout the study and up to 24 weeks after planned end of treatment. An investigator who is a qualified physician evaluated digestive disorders causality and severity. Only grade 1 or 2 were reported. No grade 3. Grade was evaluated with table 9 of protocol.</description>
        <time_frame>Between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks</time_frame>
        <population>117 patients were included and 5 patients were excluded from the analysis because of non genotype 1b. 112 patients were analysed in modified intention to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Patients Treated With Elbasvir/Grazoprevir</title>
            <description>All patients were treated by Elbasvir / Grazoprevir. Digestive disorders are one of the most important adverse event reported</description>
          </group>
        </group_list>
        <measure>
          <title>Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Digestive Disorders Reported</title>
          <description>Digestive disorders is defined by an acceleration, a slowing down or a disturbance of the intestinal transit with or without pain. Digestive disorders were monitored throughout the study and up to 24 weeks after planned end of treatment. An investigator who is a qualified physician evaluated digestive disorders causality and severity. Only grade 1 or 2 were reported. No grade 3. Grade was evaluated with table 9 of protocol.</description>
          <population>117 patients were included and 5 patients were excluded from the analysis because of non genotype 1b. 112 patients were analysed in modified intention to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects Who Attain SVR at 4 Weeks After Cessation of Treatment (SVR4)</title>
        <description>blood samples were collected at 4 weeks after cessation of treatment and HCV RNA was measured using local laboratories tests</description>
        <time_frame>at 4 weeks after cessation of treatment</time_frame>
        <population>117 patients were enrolled. 5 patients were excluded from the analysis because they were non genotype 1b. 112 patients were analysed in modified intention to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Elbasvir/Grazoprevir</title>
            <description>Elbasvir/Grazoprevir Fixed Dose Combination: Evaluate the efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects Who Attain SVR at 4 Weeks After Cessation of Treatment (SVR4)</title>
          <description>blood samples were collected at 4 weeks after cessation of treatment and HCV RNA was measured using local laboratories tests</description>
          <population>117 patients were enrolled. 5 patients were excluded from the analysis because they were non genotype 1b. 112 patients were analysed in modified intention to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="111"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects Who Attain SVR 24 Weeks After Cessation of Treatment (SVR 24)</title>
        <description>blood samples were collected at 24 weeks after cessation of treatment and HCV RNA was measured using local laboratories tests</description>
        <time_frame>at 24 weeks after cessation of treatment</time_frame>
        <population>117 patients were included; 5 patients were excluded from the analysis population because they were non genotype 1b and one patient is lost to follow up 24 weeks after cessation of treatment. 111 patients were analysed in modified intention to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Elbasvir/Grazoprevir</title>
            <description>Elbasvir/Grazoprevir Fixed Dose Combination: Evaluate the efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects Who Attain SVR 24 Weeks After Cessation of Treatment (SVR 24)</title>
          <description>blood samples were collected at 24 weeks after cessation of treatment and HCV RNA was measured using local laboratories tests</description>
          <population>117 patients were included; 5 patients were excluded from the analysis population because they were non genotype 1b and one patient is lost to follow up 24 weeks after cessation of treatment. 111 patients were analysed in modified intention to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="106"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Virologic Failure</title>
        <description>patient with HCV RNA &gt; low limit of quantification in two different consecutive blood samples were considered as relapser</description>
        <time_frame>at 12 weeks after cessation of treatment</time_frame>
        <population>117 patients were enrolled. 5 patients were excluded from the analysis because they were non genotype 1b. 112 patients were analysed in modified intention to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Elbasvir/Grazoprevir</title>
            <description>Elbasvir/Grazoprevir Fixed Dose Combination: Evaluate the efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Virologic Failure</title>
          <description>patient with HCV RNA &gt; low limit of quantification in two different consecutive blood samples were considered as relapser</description>
          <population>117 patients were enrolled. 5 patients were excluded from the analysis because they were non genotype 1b. 112 patients were analysed in modified intention to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Evaluation of the Emergence of Viral Resistance to EBV/GZR at 24 Weeks After Cessation of Treatment</title>
        <description>Patients with HCV RNA&gt; low limit of quantification in two consecutive blood samples were considered as relapsers.</description>
        <time_frame>at 24 weeks after end of treatment</time_frame>
        <population>111 patients were analysed in modified intention to treat (5 were non genotype 1b and one was lost to follow up at week 24 after the end of treatment)</population>
        <group_list>
          <group group_id="O1">
            <title>Elbasvir/Grazoprevir</title>
            <description>Elbasvir/Grazoprevir Fixed Dose Combination: Evaluate the efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).</description>
          </group>
        </group_list>
        <measure>
          <title>Evaluation of the Emergence of Viral Resistance to EBV/GZR at 24 Weeks After Cessation of Treatment</title>
          <description>Patients with HCV RNA&gt; low limit of quantification in two consecutive blood samples were considered as relapsers.</description>
          <population>111 patients were analysed in modified intention to treat (5 were non genotype 1b and one was lost to follow up at week 24 after the end of treatment)</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>adverse events were collected between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Elbasvir/Grazoprevir</title>
          <description>Elbasvir/Grazoprevir Fixed Dose Combination: Evaluate the efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="117"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>FRACTURE OF ANATOMICAL NECK OF HUMERUS</sub_title>
                <description>FRACTURE OF ANATOMICAL NECK OF HUMERUS</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="117"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>MELANCHOLIA</sub_title>
                <description>MELANCHOLIA WITH DELIRIUM</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>ATTEMPTED SUICIDE</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="117"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="69" subjects_at_risk="117"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>DIGESTIVE DISORDERS</sub_title>
                <counts group_id="E1" events="19" subjects_affected="19" subjects_at_risk="117"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>ASTHENIA</sub_title>
                <counts group_id="E1" events="25" subjects_affected="25" subjects_at_risk="117"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" events="25" subjects_affected="25" subjects_at_risk="117"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>5 patients were non genotype 1b so they were excluded from the analysis. Patients must have genotype 1b and non severe fibrosis to be treated by 8 weeks elbasvir grazoprevir</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Armand Abergel</name_or_title>
      <organization>CHU Clermont-Ferrand</organization>
      <phone>+33473750523</phone>
      <email>aabergel@chu-clermontferrand.fr</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/NCT02973503
org study id: CHU-0285
secondary id: 2016-001363-37
nct id: NCT02973503
lead sponsor: 
collaborator: 
A Phase 3, Global, Multicenter, Open-Label Study to Investigate the Efficacy of
      Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected
      Patients, with non-severe fibrosis

      The primary objectives of this study are as follows:

        -  To evaluate the efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in
           Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by
           the proportion of subjects with sustained viral response 12 weeks after cessation of
           treatment (SVR 12).

        -  To evaluate the safety and tolerability of EBV/GZR treatment

      The secondary objectives of this study are as follows:

        -  To determine the proportion of subjects who attain SVR at 4 and 24 weeks after cessation
           of treatment (SVR4 and SVR24)

        -  To evaluate the proportion of subjects with virologic failure

        -  To evaluate the kinetics of circulating HCV RNA during treatment and after cessation of
           treatment.

        -  To evaluate the emergence of viral resistance to EBV/GZR during treatment and after
           cessation of treatment
One hundred twenty treatment-naïve subjects with chronic HCV GT1b infection without cirrhosis
      will be enrolled.

      There will be one treatment group with EBV/GZR (50/100 mg) once daily without regards to food
      for 8 weeks.

      EBV/GZR is manufactured as a 50/100 mg tablet for oral administration. Subjects will take 1
      tablet daily.

      Screening assessments will be completed within 28 days of the Day 1 visit. The screening
      window can be extended to 42 days for subjects requiring a liver biopsy, or extenuating
      circumstances.

      All subjects will complete the following study visits: Screening, Day 1, and on-treatment
      visits at the end of week 2, week 4 and week 8.

      Post-treatment visits will occur at Weeks 4, 12, and 24 after last dose of study drug. All
      subjects will complete the posttreatment Week 4 and 12 visits. Subjects who achieve SVR12
      (HCV RNA < LLOQ at posttreatment Week12) will complete the posttreatment Week 24 visit.

      Screening assessments will include physical examination, medical history, height, weight,
      vital signs, adverse events related to screening procedures, concomitant medications, safety
      laboratory tests (including hematology, chemistry, and coagulation), HCV RNA, serology (HCV,
      HBV), serology and/or antigen testing for HIV, HCV genotyping, hemoglobin A1c (HbA1c),
      assessment of the absence of cirrhosis or severe fibrosis (including Fibrotest® and
      Fibroscan®), serum β-human chorionic gonadotropin (β-hCG) (females of child-bearing potential
      only), urinalysis.

      On-treatment assessments include adverse events (AEs), concomitant medications, study
      medication dispensation and pill count, physical examination, weight, vital signs, safety
      laboratory tests, HCV RNA, and urine pregnancy tests (females of child bearing potential
      only).

      Post-treatment assessments include AEs, concomitant medications, vital signs, safety
      laboratory tests (including hematology, chemistry, and coagulation), HCV RNA, and urine
      pregnancy tests (females of child-bearing potential only).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Evaluation of the Efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve as Measured by the Proportion of Subjects With Sustained Viral Response 12 Weeks After Cessation of Treatment (SVR 12).
time frame: at 12 weeks post-treatment
description: Blood samples for HCV RNA determination were collected 12 weeks after cessation of treatment and analysed by local laboratories tests
measure: Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Asthenia Reported
time frame: Between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks
description: Asthenia was defined by abnormal physical weakness or lack of energy. Asthenia was monitored throughout the study and up to 24 weeks after planned end of treatment. An investigator who is a qualified physician evaluated all adverse events, causality and severity. Only grade 1 or 2 were reported. No grade 3. Grade was evaluated with table 9 of protocol.
measure: Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Headache Reported
time frame: between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks
description: Headache is defined by pain felt in the cranial box. Headache was monitored throughout the study and up to 24 weeks after planned end of treatment. An investigator who is a qualified physician evaluated all adverse events, causality and severity. Only grade 1 or 2 were reported. No grade 3. grade was evaluated with table 9 of protocol.
measure: Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Digestive Disorders Reported
time frame: Between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks
description: Digestive disorders is defined by an acceleration, a slowing down or a disturbance of the intestinal transit with or without pain. Digestive disorders were monitored throughout the study and up to 24 weeks after planned end of treatment. An investigator who is a qualified physician evaluated digestive disorders causality and severity. Only grade 1 or 2 were reported. No grade 3. Grade was evaluated with table 9 of protocol.
measure: Percentage of Subjects Who Attain SVR at 4 Weeks After Cessation of Treatment (SVR4)
time frame: at 4 weeks after cessation of treatment
description: blood samples were collected at 4 weeks after cessation of treatment and HCV RNA was measured using local laboratories tests
measure: Percentage of Subjects Who Attain SVR 24 Weeks After Cessation of Treatment (SVR 24)
time frame: at 24 weeks after cessation of treatment
description: blood samples were collected at 24 weeks after cessation of treatment and HCV RNA was measured using local laboratories tests
measure: Percentage of Subjects With Virologic Failure
time frame: at 12 weeks after cessation of treatment
description: patient with HCV RNA > low limit of quantification in two different consecutive blood samples were considered as relapser
measure: Evaluation of the Emergence of Viral Resistance to EBV/GZR at 24 Weeks After Cessation of Treatment
time frame: at 24 weeks after end of treatment
description: Patients with HCV RNA> low limit of quantification in two consecutive blood samples were considered as relapsers.
arm group label: Elbasvir/Grazoprevir
arm group type: Experimental
description: evaluate the efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).
intervention type: Drug
intervention name: Elbasvir/Grazoprevir Fixed Dose Combination
description: Evaluate the efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).
arm group label: Elbasvir/Grazoprevir
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Armand ABERGEL
role: Principal Investigator
affiliation: University Hospital, Clermont-Ferrand
last name: Isabelle FOUCHART-HUBERT
role: Principal Investigator
affiliation: University Hospital, Angers
last name: Vincent DI MARTINO
role: Principal Investigator
affiliation: Centre Hospitalier Universitaire de Besancon
last name: Véronique LOUSTAUD RATTI
role: Principal Investigator
affiliation: CHU LIMOGES
last name: Jérôme GOURNAY
role: Principal Investigator
affiliation: CHU Nantes
last name: Tarik ASSELAH
role: Principal Investigator
affiliation: Hôpital Beaujon
last name: Didier SAMUEL
role: Principal Investigator
affiliation: Hôpital Paul Brousse
last name: Dominique LARREY
role: Principal Investigator
affiliation: University Hospital, Montpellier
last name: Sophie METIVIER
role: Principal Investigator
affiliation: CHU Toulouse Hopital Purpan
last name: Christophe HEZODE
role: Principal Investigator
affiliation: CHU Henri Mondor
last name: Albert TRAN
role: Principal Investigator
affiliation: CHU Nice hopital Archet II
last name: François BAILLY
role: Principal Investigator
affiliation: Hospice civils de Lyon, hopital de la croix Rousse
last name: Stanislas POL
role: Principal Investigator
affiliation: AP-HP Hopital Cochin
last name: Valérie CANVA
role: Principal Investigator
affiliation: CHU de Lille
facility: 
country: France
responsible party type: Sponsor
mesh term: Hepatitis C
mesh term: Fibrosis
mesh term: Grazoprevir
mesh term: Elbasvir-grazoprevir drug combination
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: 5 patients were non genotype 1b so they were excluded from the analysis. Patients must have genotype 1b and non severe fibrosis to be treated by 8 weeks elbasvir grazoprevir
point of contact: 