<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/NCT03032666</url>
  </required_header>
  <id_info>
    <org_study_id>IM.AS1.47</org_study_id>
    <nct_id>NCT03032666</nct_id>
  </id_info>
  <brief_title>Sofosbuvir/Ledipasvir for Hepatitis C Genotype 1-6 in Patients With Transfusion-Dependent Thalassemia: An Open Label Trial</brief_title>
  <official_title>Sofosbuvir/Ledipasvir for Hepatitis C Genotype 1-6 in Patients With Transfusion-Dependent Thalassemia: An Open Label Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ala'a Sharara</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>American University of Beirut Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Sustained Viral Response following 12-week therapy (SVR 12) with sofosbuvir/ledipasvir in&#xD;
      transfusion-dependent patients with HCV genotype 1-6&#xD;
&#xD;
      Secondary Objective(s):&#xD;
&#xD;
      Assessment of transfusion requirements Adverse events Efficacy in treatment-naïve vs.&#xD;
      relapsers vs. null responders Efficacy in patients with advanced fibrosis/cirrhosis vs. F1,&#xD;
      F2 by elastography&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Thalassemia is characterized by a defect in red blood cell production. The anemia is caused&#xD;
      by destruction of the erythroblasts in the bone marrow, erythrocytes' hemolysis and disrupted&#xD;
      erythropoiesis. The life-long need for transfusions makes patients vulnerable to transfusion&#xD;
      transmitted viral infections especially hepatitis C virus (HCV). HCV infection is a&#xD;
      widespread disease. It affects a large number of thalassemia patients and it is considered a&#xD;
      major public health problem. Infection with HCV results in chronic infection in a huge&#xD;
      proportion of infected individuals. Therefore, it has been suggested that early treatment of&#xD;
      acute HCV may prevent the development of chronic hepatitis.&#xD;
&#xD;
      Several studies have dwelled on the efficacy of interferon therapy for acute HCV infection in&#xD;
      adults. Newer pegylated interferons (PEG-IFN) were used in the treatment of adults with acute&#xD;
      HCV which showed equally excellent results. However, in thalassemia patients, iron overload&#xD;
      in the liver negatively affects the outcome of liver disease leading to more severe hepatic&#xD;
      inflammation and fibrosis in chronic hepatitis C which decreases response to IFN therapy.&#xD;
&#xD;
      Ribavarin has also been added as a treatment option with IFN, but ribavirin in thalassemia&#xD;
      patients increases transfusion need by a median of 30-40 %, but does not increase major&#xD;
      adverse events or treatment withdrawal.&#xD;
&#xD;
      At the end of 2013, the Food and Drug Administration (FDA) approved a new direct-acting&#xD;
      antiviral agent for the treatment of HCV infection: Sofosbuvir (Gilead Sciences). Ledipasvir&#xD;
      (Gilead Sciences) is a new drug with potent activity against HCV genotypes 1a and 1b. The&#xD;
      combination of ledipasvir and sofosbuvir resulted in high rates of response among patients&#xD;
      with HCV genotype 1 infection who had received prior treatment with interferon-based&#xD;
      regimens. Ledipasvir and sofosbuvir have been combined in a single fixed-dose tablet for use&#xD;
      once daily (ledipasvir-sofosbuvir).&#xD;
&#xD;
      Using this drug for HCV therapy alone or in combination with IFN for 12 or 24 weeks, resulted&#xD;
      in more than 90% response rates in patients from the general population.&#xD;
&#xD;
      Patients with transfusion-dependent thalassemia major are at increased risk of adverse events&#xD;
      with pegylated interferon and ribavirin therapy for HCV due to a notable 30% increase in&#xD;
      transfusion requirements during the 48-week therapy. Some patients are not eligible for other&#xD;
      treatments as they relapsed or did not respond to previous Ribavarin and IFN regimens.&#xD;
      Treatment naïve thalassemia patients with HCV will be exposed to anemia and&#xD;
      transfusion-induced iron overload among other adverse events associated with Ribavarin and&#xD;
      IFN. These patients in particular, in addition to treatment-naïve thalassemia patients, have&#xD;
      limited alternative treatment options available and constitute an area of significant unmet&#xD;
      clinical needs. There is currently no literature available showing the efficacy of&#xD;
      sofosbuvir/ledipasvir in the treatment of thalassemia patients with hepatitis C. Therefore,&#xD;
      this trial will study the efficacy of sofosbuvir/ledipasvir for hepatitis C genotype 1-6 in&#xD;
      patients with transfusion-dependent thalassemia.&#xD;
&#xD;
      Ten patients from the Lebanese Chronic Care Center will be enrolled in this open label trial.&#xD;
      Patients with transfusion dependent thalassemia with hepatitis C will be enrolled. Study&#xD;
      patients will receive the treatment following informed consent and will be followed up&#xD;
      regularly by the study coordinator for side effects, compliance and adherence. A blood test&#xD;
      for hemoglobin and hematocrit and liver enzyme, will be done on all patients at baseline and&#xD;
      then after 4 weeks, 8 weeks , and 12 weeks of therapy. At week 12, levels of the virus in the&#xD;
      patient's blood will also be evaluated. Liver imaging will be done throughout the study.&#xD;
&#xD;
      Benefits of this study outweigh potential risks. Side effects of medications used are minor&#xD;
      however potential benefits for the patients are possibly treating their hepatitis C with an&#xD;
      approved drug (in the general population) at no cost, and for the society, the possibility of&#xD;
      finding an oral treatment more efficient and tolerable in this special population.&#xD;
&#xD;
      As for privacy and confidentiality issues, all data will be under lock. The PI and the Co-&#xD;
      Investigators will be the only ones with access to that data.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2017</start_date>
  <completion_date type="Actual">August 6, 2018</completion_date>
  <primary_completion_date type="Actual">August 6, 2018</primary_completion_date>
  <phase>Phase 4</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>Sustained Viral Response following 12-week therapy (SVR 12) with sofosbuvir/velpatasvir in transfusion-dependent patients with HCV genotype 1-6</measure>
    <time_frame>12 weeks</time_frame>
    <description>Via tests of HepC RNA levels</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Thalassemia</condition>
  <condition>Hepatitis C</condition>
  <arm_group>
    <arm_group_label>sofosbuvir/velpatasvir</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Epclusa</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sofosbuvir/velpatasvir</intervention_name>
    <description>treatment of hepatitis C genotype 1-6 in patients with transfusion-dependent thalassemia.</description>
    <arm_group_label>sofosbuvir/velpatasvir</arm_group_label>
    <other_name>Epclusa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Transfusion Dependent thalassemia patients with HCV genotype 1-6&#xD;
&#xD;
          -  Age ≥18&#xD;
&#xD;
          -  Male and female&#xD;
&#xD;
          -  No evidence of hepatocellular carcinoma on ultrasound&#xD;
&#xD;
          -  No known drug allergy to the FDA approved drug to be used&#xD;
&#xD;
          -  Adequate iron chelation therapy&#xD;
&#xD;
          -  Compensated liver disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age below 18&#xD;
&#xD;
          -  Chronic HCV genotypes 2 or 3&#xD;
&#xD;
          -  Allergy to study drug&#xD;
&#xD;
          -  Hepatocellular carcinoma&#xD;
&#xD;
          -  Inadequate iron chelation therapy&#xD;
&#xD;
          -  Decompensated liver disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>American University of Beirut Medical Center</name>
      <address>
        <city>Beirut</city>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Lebanon</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>October 10, 2018</last_update_submitted>
  <last_update_submitted_qc>October 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>American University of Beirut Medical Center</investigator_affiliation>
    <investigator_full_name>Ala'a Sharara</investigator_full_name>
    <investigator_title>Professor, Head of Gastroenterology Department</investigator_title>
  </responsible_party>
  <keyword>Thalassemia</keyword>
  <keyword>HCV</keyword>
  <keyword>Sofosbuvir</keyword>
  <keyword>Ledipasvir</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Thalassemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sofosbuvir</mesh_term>
    <mesh_term>Sofosbuvir-velpatasvir drug combination</mesh_term>
    <mesh_term>Velpatasvir</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/NCT03032666
org study id: IM.AS1.47
nct id: NCT03032666
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Sustained Viral Response following 12-week therapy (SVR 12) with sofosbuvir/ledipasvir in
      transfusion-dependent patients with HCV genotype 1-6

      Secondary Objective(s):

      Assessment of transfusion requirements Adverse events Efficacy in treatment-naïve vs.
      relapsers vs. null responders Efficacy in patients with advanced fibrosis/cirrhosis vs. F1,
      F2 by elastography
Thalassemia is characterized by a defect in red blood cell production. The anemia is caused
      by destruction of the erythroblasts in the bone marrow, erythrocytes' hemolysis and disrupted
      erythropoiesis. The life-long need for transfusions makes patients vulnerable to transfusion
      transmitted viral infections especially hepatitis C virus (HCV). HCV infection is a
      widespread disease. It affects a large number of thalassemia patients and it is considered a
      major public health problem. Infection with HCV results in chronic infection in a huge
      proportion of infected individuals. Therefore, it has been suggested that early treatment of
      acute HCV may prevent the development of chronic hepatitis.

      Several studies have dwelled on the efficacy of interferon therapy for acute HCV infection in
      adults. Newer pegylated interferons (PEG-IFN) were used in the treatment of adults with acute
      HCV which showed equally excellent results. However, in thalassemia patients, iron overload
      in the liver negatively affects the outcome of liver disease leading to more severe hepatic
      inflammation and fibrosis in chronic hepatitis C which decreases response to IFN therapy.

      Ribavarin has also been added as a treatment option with IFN, but ribavirin in thalassemia
      patients increases transfusion need by a median of 30-40 %, but does not increase major
      adverse events or treatment withdrawal.

      At the end of 2013, the Food and Drug Administration (FDA) approved a new direct-acting
      antiviral agent for the treatment of HCV infection: Sofosbuvir (Gilead Sciences). Ledipasvir
      (Gilead Sciences) is a new drug with potent activity against HCV genotypes 1a and 1b. The
      combination of ledipasvir and sofosbuvir resulted in high rates of response among patients
      with HCV genotype 1 infection who had received prior treatment with interferon-based
      regimens. Ledipasvir and sofosbuvir have been combined in a single fixed-dose tablet for use
      once daily (ledipasvir-sofosbuvir).

      Using this drug for HCV therapy alone or in combination with IFN for 12 or 24 weeks, resulted
      in more than 90% response rates in patients from the general population.

      Patients with transfusion-dependent thalassemia major are at increased risk of adverse events
      with pegylated interferon and ribavirin therapy for HCV due to a notable 30% increase in
      transfusion requirements during the 48-week therapy. Some patients are not eligible for other
      treatments as they relapsed or did not respond to previous Ribavarin and IFN regimens.
      Treatment naïve thalassemia patients with HCV will be exposed to anemia and
      transfusion-induced iron overload among other adverse events associated with Ribavarin and
      IFN. These patients in particular, in addition to treatment-naïve thalassemia patients, have
      limited alternative treatment options available and constitute an area of significant unmet
      clinical needs. There is currently no literature available showing the efficacy of
      sofosbuvir/ledipasvir in the treatment of thalassemia patients with hepatitis C. Therefore,
      this trial will study the efficacy of sofosbuvir/ledipasvir for hepatitis C genotype 1-6 in
      patients with transfusion-dependent thalassemia.

      Ten patients from the Lebanese Chronic Care Center will be enrolled in this open label trial.
      Patients with transfusion dependent thalassemia with hepatitis C will be enrolled. Study
      patients will receive the treatment following informed consent and will be followed up
      regularly by the study coordinator for side effects, compliance and adherence. A blood test
      for hemoglobin and hematocrit and liver enzyme, will be done on all patients at baseline and
      then after 4 weeks, 8 weeks , and 12 weeks of therapy. At week 12, levels of the virus in the
      patient's blood will also be evaluated. Liver imaging will be done throughout the study.

      Benefits of this study outweigh potential risks. Side effects of medications used are minor
      however potential benefits for the patients are possibly treating their hepatitis C with an
      approved drug (in the general population) at no cost, and for the society, the possibility of
      finding an oral treatment more efficient and tolerable in this special population.

      As for privacy and confidentiality issues, all data will be under lock. The PI and the Co-
      Investigators will be the only ones with access to that data.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Sustained Viral Response following 12-week therapy (SVR 12) with sofosbuvir/velpatasvir in transfusion-dependent patients with HCV genotype 1-6
time frame: 12 weeks
description: Via tests of HepC RNA levels
arm group label: sofosbuvir/velpatasvir
arm group type: Experimental
description: Epclusa
intervention type: Drug
intervention name: sofosbuvir/velpatasvir
description: treatment of hepatitis C genotype 1-6 in patients with transfusion-dependent thalassemia.
arm group label: sofosbuvir/velpatasvir
other name: Epclusa
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
facility: 
country: Lebanon
responsible party type: Sponsor-Investigator
investigator affiliation: American University of Beirut Medical Center
investigator full name: Ala'a Sharara
investigator title: Professor, Head of Gastroenterology Department
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis
mesh term: Thalassemia
mesh term: Sofosbuvir
mesh term: Sofosbuvir-velpatasvir drug combination
mesh term: Velpatasvir
sharing ipd: No