<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/NCT03250910</url>
  </required_header>
  <id_info>
    <org_study_id>201602026RINC</org_study_id>
    <nct_id>NCT03250910</nct_id>
  </id_info>
  <brief_title>Generic VEL/SOF With or Without RBV for HIV/HCV Coinfected Patients</brief_title>
  <official_title>Generic Velpatasvir Plus Sofosbuvir With or Without Ribavirin for the Treatment of Hepatitis C Virus in Patients Coinfected With Human Immunodeficiency Virus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</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>
      Data are limited regarding the effectiveness and safety of generic velpatasvir plus&#xD;
      sofosbuvir (VEL/SOF) with or without ribavirin (RBV) for the treatment of hepatitis C virus&#xD;
      (HCV) in patients with human immunodeficiency virus (HIV) coinfection. We aim to compare the&#xD;
      effectiveness and safety of VEL/SOF with and without RBV for 12 weeks in HIV/HCV-coinfected&#xD;
      and HCV-monoinfected patients The antiviral responses and the adverse events (AEs) are&#xD;
      compare between the two groups. The characteristics potentially related to sustained&#xD;
      virologic response 12 weeks off therapy (SVR12) are analyzed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Due to the lack of effective vaccination and the shared routes of transmission, hepatitis C&#xD;
      virus (HCV) infection remains a challenging co-morbidity in patients with human&#xD;
      immunodeficiency virus (HIV) infection. It is estimated that approximately 2.3 million people&#xD;
      are coinfected with HIV and HCV (HIV/HCV) in the world. Compared to patients with HCV&#xD;
      monoinfection, HIV/HCV-coinfected patients tend to have higher serum HCV viral loads, faster&#xD;
      hepatic fibrosis progression, and higher risks of hepatic decompensation. Following the&#xD;
      commencement of scale-up antiretroviral therapy (ART) that decreases the HIV-related&#xD;
      opportunistic infections and malignancies, the liver-related complications have now become&#xD;
      the leading cause of morbidity and mortality in HIV/HCV-coinfected patients. On the other&#xD;
      hand, the survival rate is improved if these patients achieve sustained virologic response&#xD;
      (SVR) by anti-HCV agents.&#xD;
&#xD;
      On the basis of excellent efficacy and safety, treatment by interferon (IFN)-free direct&#xD;
      acting antiviral agents (DAAs) has made a paradigm shift for HCV care. Velpatasvir (VEL) is&#xD;
      an HCV non-structural protein 5A (NS5A) inhibitor and sofosbuvir (SOF) is an HCV NS5B&#xD;
      nucleotide polymerase inhibitor. Both agents are active against HCV with pan-genotypic&#xD;
      potency. A fixed-dose combination of VEL at a daily dosage of 100 mg and SOF at a daily&#xD;
      dosage of 400 mg (VEL/SOF) with or without weight-based ribavirin (RBV) has been approved by&#xD;
      U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) to treat HCV&#xD;
      genotype 1-6 patients with compensated and decompensated liver diseases, respectively.&#xD;
      Recently, a phase 3 study of VEL/SOF to treat HCV infection in HIV-coinfected patients&#xD;
      reveals that this regimen is safe and provides a high and comparable SVR rate to&#xD;
      HCV-monoinfected patients.&#xD;
&#xD;
      Although treatment of HCV by IFN-free DAAs is considered highly efficacious and well&#xD;
      tolerated, numerous HCV-infected individuals have limited access to the brand-name agents due&#xD;
      to the lack of universal governmental reimbursement or private insurance support. Therefore,&#xD;
      allowing the generic version of patented DAAs for HCV through voluntary or compulsory&#xD;
      licensing may provide patients with greater access to new HCV treatment, particularly in&#xD;
      resource-constrained countries. Regarding the real-world experiences of generic IFN-free&#xD;
      DAAs, a recent report from China evaluated the effectiveness of a generic version of&#xD;
      ledipasvir (LDV) plus SOF (LDV/SOF) with or without RBV for 8-12 weeks in 192 HCV genotype 1b&#xD;
      (HCV-1b) patients. The overall SVR rates were excellent (96.8%-96.9%) and most patients&#xD;
      tolerated the treatment well. Based on the encouraging results, we aim to evaluate the&#xD;
      effectiveness and safety of a generic version of pan-genotypic VEL/SOF-based therapy for HCV&#xD;
      in HIV-coinfected patients, and compare the performance of such a regimen in HCV-monoinfected&#xD;
      patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2016</start_date>
  <completion_date type="Actual">October 31, 2017</completion_date>
  <primary_completion_date type="Actual">July 15, 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sustained virologic response</measure>
    <time_frame>24 weeks</time_frame>
    <description>HCV RNA &lt; LLOQ 12 weeks off therapy</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">228</enrollment>
  <condition>Hepatitis C Virus Infection, Response to Therapy of</condition>
  <condition>Human Immunodeficiency Virus</condition>
  <arm_group>
    <arm_group_label>HIV/HCV compensated liver disease</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) received a generic version of Sofosbuvir and Velpatasvir fixed-dose combination (Sofosvel®, VEL/SOF 100/400 mg film coated tablet, Beacon Pharmaceuticals Ltd. Mymensingh, Bangladesh) 1 tablet per day for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV/HCV decompensated liver disease</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with decompensated cirrhosis (Child-Pugh B or C) received Sofosvel® 1 tablet per day in combination with weight-based ribavirin (RBV)(Robatrol®, 200 mg capsule, Genovate Biotechnology Co. Ltd., Hsinchu, Taiwan; 1,200 mg per day if the body weight ≥ 75 kg; 1,000 mg per day if the body weight &lt; 75 mg) for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HCV compensated liver disease</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) received a generic version of Sofosbuvir and Velpatasvir fixed-dose combination (Sofosvel®, VEL/SOF 100/400 mg film coated tablet, Beacon Pharmaceuticals Ltd. Mymensingh, Bangladesh) 1 tablet per day for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HCV decompensated liver disease</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with decompensated cirrhosis (Child-Pugh B or C) received Sofosvel® 1 tablet per day in combination with weight-based ribavirin (RBV)(Robatrol®, 200 mg capsule, Genovate Biotechnology Co. Ltd., Hsinchu, Taiwan; 1,200 mg per day if the body weight ≥ 75 kg; 1,000 mg per day if the body weight &lt; 75 mg) for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sofosbuvir and Velpatasvir</intervention_name>
    <description>All patients received a generic version of VEL/SOF fixed-dose combination (Sofosvel®, VEL/SOF 100/400 mg film coated tablet, Beacon Pharmaceuticals Ltd. Mymensingh, Bangladesh) 1 tablet per day for 12 weeks.</description>
    <arm_group_label>HCV compensated liver disease</arm_group_label>
    <arm_group_label>HCV decompensated liver disease</arm_group_label>
    <arm_group_label>HIV/HCV compensated liver disease</arm_group_label>
    <arm_group_label>HIV/HCV decompensated liver disease</arm_group_label>
    <other_name>Sofosvel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ribavirin</intervention_name>
    <description>Patients with decompensated cirrhosis (Child-Pugh B or C), received weight-based ribavirin (RBV)(Robatrol®, 200 mg capsule, Genovate Biotechnology Co. Ltd., Hsinchu, Taiwan; 1,200 mg per day if the body weight ≥ 75 kg; 1,000 mg per day if the body weight &lt; 75 mg) for 12 weeks.</description>
    <arm_group_label>HCV decompensated liver disease</arm_group_label>
    <arm_group_label>HIV/HCV decompensated liver disease</arm_group_label>
    <other_name>Robatrol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; or = 20 years&#xD;
&#xD;
          -  Chronic HCV infection, defined as detectable HCV antibody (anti-HCV; Abbott HCV EIA&#xD;
             2.0, Abbott Laboratories, Abbott Park, Illinois, USA) and quantifiable serum HCV RNA&#xD;
             (Cobas TaqMan HCV Test v2.0, Roche Diagnostics GmbH, Mannheim, Germany, lower limit of&#xD;
             quantification [LLOQ]: 25 IU/mL) for ≥ 6 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic kidney disease (CKD) stage ≥ 4,&#xD;
&#xD;
          -  Organ transplantation&#xD;
&#xD;
          -  Prior DAA exposure&#xD;
&#xD;
          -  Refusal to provide written informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chen-Hua Liu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Taiwan University Hospital, Yun-Lin Branch</name>
      <address>
        <city>Douliu</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>December 6, 2017</last_update_submitted>
  <last_update_submitted_qc>December 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hepatitis C virus</keyword>
  <keyword>human immunodeficiency virus</keyword>
  <keyword>Direct acting antiviral agent</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ribavirin</mesh_term>
    <mesh_term>Sofosbuvir</mesh_term>
    <mesh_term>Velpatasvir</mesh_term>
    <mesh_term>Sofosbuvir-velpatasvir drug combination</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/NCT03250910
org study id: 201602026RINC
nct id: NCT03250910
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Data are limited regarding the effectiveness and safety of generic velpatasvir plus
      sofosbuvir (VEL/SOF) with or without ribavirin (RBV) for the treatment of hepatitis C virus
      (HCV) in patients with human immunodeficiency virus (HIV) coinfection. We aim to compare the
      effectiveness and safety of VEL/SOF with and without RBV for 12 weeks in HIV/HCV-coinfected
      and HCV-monoinfected patients The antiviral responses and the adverse events (AEs) are
      compare between the two groups. The characteristics potentially related to sustained
      virologic response 12 weeks off therapy (SVR12) are analyzed.
Due to the lack of effective vaccination and the shared routes of transmission, hepatitis C
      virus (HCV) infection remains a challenging co-morbidity in patients with human
      immunodeficiency virus (HIV) infection. It is estimated that approximately 2.3 million people
      are coinfected with HIV and HCV (HIV/HCV) in the world. Compared to patients with HCV
      monoinfection, HIV/HCV-coinfected patients tend to have higher serum HCV viral loads, faster
      hepatic fibrosis progression, and higher risks of hepatic decompensation. Following the
      commencement of scale-up antiretroviral therapy (ART) that decreases the HIV-related
      opportunistic infections and malignancies, the liver-related complications have now become
      the leading cause of morbidity and mortality in HIV/HCV-coinfected patients. On the other
      hand, the survival rate is improved if these patients achieve sustained virologic response
      (SVR) by anti-HCV agents.

      On the basis of excellent efficacy and safety, treatment by interferon (IFN)-free direct
      acting antiviral agents (DAAs) has made a paradigm shift for HCV care. Velpatasvir (VEL) is
      an HCV non-structural protein 5A (NS5A) inhibitor and sofosbuvir (SOF) is an HCV NS5B
      nucleotide polymerase inhibitor. Both agents are active against HCV with pan-genotypic
      potency. A fixed-dose combination of VEL at a daily dosage of 100 mg and SOF at a daily
      dosage of 400 mg (VEL/SOF) with or without weight-based ribavirin (RBV) has been approved by
      U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) to treat HCV
      genotype 1-6 patients with compensated and decompensated liver diseases, respectively.
      Recently, a phase 3 study of VEL/SOF to treat HCV infection in HIV-coinfected patients
      reveals that this regimen is safe and provides a high and comparable SVR rate to
      HCV-monoinfected patients.

      Although treatment of HCV by IFN-free DAAs is considered highly efficacious and well
      tolerated, numerous HCV-infected individuals have limited access to the brand-name agents due
      to the lack of universal governmental reimbursement or private insurance support. Therefore,
      allowing the generic version of patented DAAs for HCV through voluntary or compulsory
      licensing may provide patients with greater access to new HCV treatment, particularly in
      resource-constrained countries. Regarding the real-world experiences of generic IFN-free
      DAAs, a recent report from China evaluated the effectiveness of a generic version of
      ledipasvir (LDV) plus SOF (LDV/SOF) with or without RBV for 8-12 weeks in 192 HCV genotype 1b
      (HCV-1b) patients. The overall SVR rates were excellent (96.8%-96.9%) and most patients
      tolerated the treatment well. Based on the encouraging results, we aim to evaluate the
      effectiveness and safety of a generic version of pan-genotypic VEL/SOF-based therapy for HCV
      in HIV-coinfected patients, and compare the performance of such a regimen in HCV-monoinfected
      patients.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Sustained virologic response
time frame: 24 weeks
description: HCV RNA < LLOQ 12 weeks off therapy
arm group label: HIV/HCV compensated liver disease
arm group type: Experimental
description: Patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) received a generic version of Sofosbuvir and Velpatasvir fixed-dose combination (Sofosvel®, VEL/SOF 100/400 mg film coated tablet, Beacon Pharmaceuticals Ltd. Mymensingh, Bangladesh) 1 tablet per day for 12 weeks.
arm group label: HIV/HCV decompensated liver disease
arm group type: Experimental
description: Patients with decompensated cirrhosis (Child-Pugh B or C) received Sofosvel® 1 tablet per day in combination with weight-based ribavirin (RBV)(Robatrol®, 200 mg capsule, Genovate Biotechnology Co. Ltd., Hsinchu, Taiwan; 1,200 mg per day if the body weight ≥ 75 kg; 1,000 mg per day if the body weight < 75 mg) for 12 weeks.
arm group label: HCV compensated liver disease
arm group type: Active Comparator
description: Patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) received a generic version of Sofosbuvir and Velpatasvir fixed-dose combination (Sofosvel®, VEL/SOF 100/400 mg film coated tablet, Beacon Pharmaceuticals Ltd. Mymensingh, Bangladesh) 1 tablet per day for 12 weeks.
arm group label: HCV decompensated liver disease
arm group type: Active Comparator
description: Patients with decompensated cirrhosis (Child-Pugh B or C) received Sofosvel® 1 tablet per day in combination with weight-based ribavirin (RBV)(Robatrol®, 200 mg capsule, Genovate Biotechnology Co. Ltd., Hsinchu, Taiwan; 1,200 mg per day if the body weight ≥ 75 kg; 1,000 mg per day if the body weight < 75 mg) for 12 weeks.
intervention type: Drug
intervention name: Sofosbuvir and Velpatasvir
description: All patients received a generic version of VEL/SOF fixed-dose combination (Sofosvel®, VEL/SOF 100/400 mg film coated tablet, Beacon Pharmaceuticals Ltd. Mymensingh, Bangladesh) 1 tablet per day for 12 weeks.
arm group label: HCV compensated liver disease
arm group label: HCV decompensated liver disease
arm group label: HIV/HCV compensated liver disease
arm group label: HIV/HCV decompensated liver disease
other name: Sofosvel
intervention type: Drug
intervention name: Ribavirin
description: Patients with decompensated cirrhosis (Child-Pugh B or C), received weight-based ribavirin (RBV)(Robatrol®, 200 mg capsule, Genovate Biotechnology Co. Ltd., Hsinchu, Taiwan; 1,200 mg per day if the body weight ≥ 75 kg; 1,000 mg per day if the body weight < 75 mg) for 12 weeks.
arm group label: HCV decompensated liver disease
arm group label: HIV/HCV decompensated liver disease
other name: Robatrol
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Chen-Hua Liu, MD
role: Principal Investigator
affiliation: National Taiwan University Hospital
facility: 
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Virus Diseases
mesh term: Hepatitis C
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Hepatitis
mesh term: Immunologic Deficiency Syndromes
mesh term: Ribavirin
mesh term: Sofosbuvir
mesh term: Velpatasvir
mesh term: Sofosbuvir-velpatasvir drug combination
sharing ipd: No