<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/NCT03282474</url>
  </required_header>
  <id_info>
    <org_study_id>HepNet-SofE</org_study_id>
    <secondary_id>2017-000403-24</secondary_id>
    <nct_id>NCT03282474</nct_id>
  </id_info>
  <brief_title>HepNet Pilot Trial: Multicenter Trial for the Treatment of Chronic Hepatitis E With Sofosbuvir (SofE)</brief_title>
  <official_title>HepNet Pilot Trial: Multicenter Trial for the Treatment of Chronic Hepatitis E With Sofosbuvir (SofE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hannover Medical School</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>HepNet Study House, German Liverfoundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>German Center for Infection Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hannover Medical School</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single arm multicenter pilot study to provide preliminary evidence whether&#xD;
      sofosbuvir (SOF) is efficacious and can be safely used in patients with chronic Hepatitis E&#xD;
      virus infection.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 7, 2017</start_date>
  <completion_date type="Actual">February 18, 2019</completion_date>
  <primary_completion_date type="Actual">November 26, 2018</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Prospective, open-label, single-arm multicenter, phase II pilot trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of subjects who become HEV RNA negative after 24 weeks of therapy</measure>
    <time_frame>after 24 weeks of therapy</time_frame>
    <description>Measured by the proportion of subjects who become HEV RNA negative (HEV RNA undetectable)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects who are HEV RNA negative 12 weeks after discontinuation of therapy</measure>
    <time_frame>12 weeks after discontinuation of therapy (week 36)</time_frame>
    <description>Viral load measurement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional efficacy evaluations include HEV RNA change from baseline during therapy</measure>
    <time_frame>after 2 days, 4 days, 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks,16 weeks, 20 weeks, and 24 weeks of therapy</time_frame>
    <description>Viral load and laboratory measurements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of proportion of patients who are HEV RNA negative after rapid or slow decline of HEV viral load after 24 weeks of therapy</measure>
    <time_frame>after 24 weeks of therapy</time_frame>
    <description>Viral load measurement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subject who reached ALT normalization after 12 weeks and 24 weeks of therapy and 12 weeks after discontinuation of therapy</measure>
    <time_frame>after 12 and 24 weeks of therapy and 12 weeks after discontinuation of therapy (week 36)</time_frame>
    <description>Laboratory measurement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of safety: Adverse events and safety laboratory tests will be collected throughout the study</measure>
    <time_frame>through study completion, an average of 36 weeks</time_frame>
    <description>Collection of adverse events and safety laboratory tests</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Hepatitis E</condition>
  <condition>Hepatitis Chronic Viral</condition>
  <arm_group>
    <arm_group_label>Sofosbuvir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sofosbuvir 400 MG film-coated tablet, oral administration of one tablet once daily for 24 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sofosbuvir</intervention_name>
    <description>Sofosbuvir 400 MG Oral Tablet [Sovaldi]</description>
    <arm_group_label>Sofosbuvir</arm_group_label>
    <other_name>Sovaldi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing and able to provide written informed consent&#xD;
&#xD;
          2. Male or female, age ≥ 18 years&#xD;
&#xD;
          3. Confirmation of chronic HEV infection documented by: Positive HEV RNA at least 3&#xD;
             months before Screening, and positive for HEV RNA at the time of Screening&#xD;
&#xD;
          4. Documented previous ribavirin therapy or documented contraindication for full dose (≥&#xD;
             600mg qd) ribavirin monotherapy for at least 3 months&#xD;
&#xD;
          5. Body mass index (BMI) ≥ 18 kg/m2&#xD;
&#xD;
          6. Screening ECG without clinically significant abnormalities&#xD;
&#xD;
          7. Subjects must have the following laboratory parameters at screening:&#xD;
&#xD;
               -  Platelets ≥ 60,000/μL&#xD;
&#xD;
               -  INR ≤2.0 x ULN unless subject has known hemophilia or is stable on an&#xD;
                  anticoagulant regimen affecting INR&#xD;
&#xD;
               -  HbA1c ≤ 10%&#xD;
&#xD;
               -  Creatinine clearance (CLcr) ≥ 30 mL/min, as calculated by the Cockcroft-Gault&#xD;
                  equation (using actual body weight)&#xD;
&#xD;
          8. Subject has not been treated with any investigational drug or device within 42 days of&#xD;
             the Screening visit&#xD;
&#xD;
          9. A negative serum pregnancy test is required for female subjects (unless surgically&#xD;
             sterile or women ≥ 54 years of age with cessation for 24 ≥ months of previously&#xD;
             occurring menses).&#xD;
&#xD;
             Complete abstinence from intercourse. Periodic abstinence (e.g., calendar, ovulation,&#xD;
             symptothermal, post-ovulation methods) is not permitted.&#xD;
&#xD;
             Or&#xD;
&#xD;
             Consistent and correct use of 1 of the following methods of birth control listed&#xD;
             below, in addition to a male partner who correctly uses a condom, from the date of&#xD;
             Screening until 30 days after last dose of study drug:&#xD;
&#xD;
               -  intrauterine device (IUD) with a failure rate of &lt; 1% per year&#xD;
&#xD;
               -  female barrier method: cervical cap or diaphragm with spermicidal agent&#xD;
&#xD;
               -  tubal sterilization&#xD;
&#xD;
               -  vasectomy in male partner&#xD;
&#xD;
               -  hormone-containing contraceptive:&#xD;
&#xD;
                    -  implants of levonorgestrel&#xD;
&#xD;
                    -  injectable progesterone&#xD;
&#xD;
                    -  oral contraceptives (either combined or progesterone only)&#xD;
&#xD;
                    -  contraceptive vaginal ring&#xD;
&#xD;
                    -  transdermal contraceptive patch&#xD;
&#xD;
         10. Subject must be able to comply with the dosing instructions for study drug&#xD;
             administration and be able to complete the study schedule of assessments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Clinically-significant illness (other than HEV) or any other major medical disorder&#xD;
             that, in the opinion of the investigator, may interfere with subject treatment,&#xD;
             assessment or compliance with the protocol.&#xD;
&#xD;
          2. Ribavirin administration within the last 28 days.&#xD;
&#xD;
          3. Infection with the hepatitis C virus (defined as HCV RNA positive)&#xD;
&#xD;
          4. Gastrointestinal disorder or post-operative condition that could interfere with the&#xD;
             absorption of the study drug (for example, gastric bypass or severe ulcerative&#xD;
             colitis).&#xD;
&#xD;
          5. Difficulty with blood collection and/or poor venous access for the purposes of&#xD;
             phlebotomy.&#xD;
&#xD;
          6. Psychiatric hospitalization, suicide attempt, and/or a period of disability as a&#xD;
             result of their psychiatric illness within the last 2 years. Subjects with psychiatric&#xD;
             illness that is wellcontrolled on a stable treatment regimen for at least 12 months&#xD;
             prior to screening or has not required medication in the last 12 months may be&#xD;
             included.&#xD;
&#xD;
          7. Significant drug allergy (such as anaphylaxis or hepatotoxicity).&#xD;
&#xD;
          8. Pregnant or nursing female&#xD;
&#xD;
          9. Clinically-relevant drug or alcohol abuse within 12 months of screening including any&#xD;
             uncontrolled drug use within 6 months of screening. A positive drug screen will&#xD;
             exclude subjects unless it can be explained by a prescribed medication; the diagnosis&#xD;
             and prescription must be approved by the investigator. Uncontrolled users of&#xD;
             intravenous drugs will not be permitted to enroll in the study.&#xD;
&#xD;
         10. Use of any prohibited concomitant medications within 21 days of the Baseline/Day 1&#xD;
             visit.&#xD;
&#xD;
             Use of Amiodaron as concomitant medication is prohibited within 60 days of&#xD;
             Baseline/Day1 visit.&#xD;
&#xD;
         11. Known hypersensitivity to SOF or formulation excipients.&#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>Markus Cornberg, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hannover Medical School, Clinic for Gastroenterology, Hepatology, and Endocrinology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hannover Medical School, Clinic for Gastroenterology, Hepatology, and Endocrinology</name>
      <address>
        <city>Hanover</city>
        <state>Lower Saxony</state>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité, Campus Virchow-Klinikum, Medical Department, Division of Hepatology and Gastroenterology</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center Hamburg-Eppendorf, Center for Internal Medicine, I. Medical Clinic and Polyclinic</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>March 7, 2019</last_update_submitted>
  <last_update_submitted_qc>March 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatitis E</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis E</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sofosbuvir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03282474
org study id: HepNet-SofE
secondary id: 2017-000403-24
nct id: NCT03282474
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a single arm multicenter pilot study to provide preliminary evidence whether
      sofosbuvir (SOF) is efficacious and can be safely used in patients with chronic Hepatitis E
      virus infection.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Prospective, open-label, single-arm multicenter, phase II pilot trial
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of subjects who become HEV RNA negative after 24 weeks of therapy
time frame: after 24 weeks of therapy
description: Measured by the proportion of subjects who become HEV RNA negative (HEV RNA undetectable)
measure: Proportion of subjects who are HEV RNA negative 12 weeks after discontinuation of therapy
time frame: 12 weeks after discontinuation of therapy (week 36)
description: Viral load measurement
measure: Additional efficacy evaluations include HEV RNA change from baseline during therapy
time frame: after 2 days, 4 days, 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks,16 weeks, 20 weeks, and 24 weeks of therapy
description: Viral load and laboratory measurements
measure: Comparison of proportion of patients who are HEV RNA negative after rapid or slow decline of HEV viral load after 24 weeks of therapy
time frame: after 24 weeks of therapy
description: Viral load measurement
measure: Proportion of subject who reached ALT normalization after 12 weeks and 24 weeks of therapy and 12 weeks after discontinuation of therapy
time frame: after 12 and 24 weeks of therapy and 12 weeks after discontinuation of therapy (week 36)
description: Laboratory measurement
measure: Assessment of safety: Adverse events and safety laboratory tests will be collected throughout the study
time frame: through study completion, an average of 36 weeks
description: Collection of adverse events and safety laboratory tests
arm group label: Sofosbuvir
arm group type: Experimental
description: Sofosbuvir 400 MG film-coated tablet, oral administration of one tablet once daily for 24 weeks.
intervention type: Drug
intervention name: Sofosbuvir
description: Sofosbuvir 400 MG Oral Tablet [Sovaldi]
arm group label: Sofosbuvir
other name: Sovaldi
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Markus Cornberg, Prof. Dr.
role: Principal Investigator
affiliation: Hannover Medical School, Clinic for Gastroenterology, Hepatology, and Endocrinology
facility: 
facility: 
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis E
mesh term: Hepatitis
mesh term: Sofosbuvir
sharing ipd: No