<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/NCT02985281</url>
  </required_header>
  <id_info>
    <org_study_id>00114/2016</org_study_id>
    <nct_id>NCT02985281</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Gratisovir (Sofosbuvir)- Ribavirin Therapy in Pediatric Patients</brief_title>
  <official_title>Safety and Efficacy of Gratisovir (Sofosbuvir)- Ribavirin Daul Therapy in Egyptian Pediatric Patients With Chronic Hepatitis C Infection. A Prospective, Randomized, Multicenter Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Liver Institute, Egypt</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pharco Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Liver Institute, Egypt</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Evaluation of Safety and Efficacy of Gratisovir (Sofosbuvir)- Ribavirin Therapy in Egyptian&#xD;
      Pediatric Patients With Chronic Hepatitis C Infection aged 10- 18 years old.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Male or female child ≥ 10 years and ≤ 18 years of age chronically infected with hepatitis C&#xD;
      virus, willing and able to complete all study visits and procedures. Acceptance from the&#xD;
      parents will be recruited for giving a verbal and written informed consent. Patient with&#xD;
      childs Pugh class B or C, compensated cirrhosis may be enrolled. Patient with cirrhosis with&#xD;
      their alpha fetoprotein is more than 100 ng/ml and patient with coinfection of Hepatitis B&#xD;
      virus or HIV will be excluded. Participation in the study procedures is anticipated to last&#xD;
      up to 40 weeks including a screening and eligibility assessment phase (4 weeks duration), a&#xD;
      24- week treatment phase, and 12- week post treatment follow up phase.&#xD;
&#xD;
      A detailed treatment log of the returned investigational product will be established with the&#xD;
      investigator (or the pharmacist) and countersigned by the investigator and the monitoring&#xD;
      team.&#xD;
&#xD;
      Compliance is assessed by counting the number of returned tablets at each visit.&#xD;
&#xD;
      A discontinuation is defined as a period with at least seven consecutive days without study&#xD;
      drug intake.&#xD;
&#xD;
      Safety and efficacy will be compared between cirrhotic versus non-cirrhotic subjects in&#xD;
      multivariate model to test the impact of this pretreatment characteristic on safety,&#xD;
      tolerability and efficacy endpoints.&#xD;
&#xD;
      Safety analysis:clinical adverse events will be displayed by body system (soc) for each study&#xD;
      subject and by treatment group, using MedDRA coding. Summary of statistics of safety and&#xD;
      efficacy endpoints will be displayed by stratification parameters.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">September 2017</completion_date>
  <primary_completion_date type="Anticipated">June 2017</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of SVR12 in both treatment groups after 12 following completion of treatment (SVR12)</measure>
    <time_frame>40 weeks including a screening and eligibility assessment phase (4 weeks duration), a 24- week treatment phase, and 12- week post treatment follow up phase.</time_frame>
    <description>incidence of SVR12 in both treatment groups after 12 weeks following completion of treatment (SVR12)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>assessment of the nature, severity and frequency of the adverse effects and absolute values and changes over time from pre-dose values for hematology clinical chemistry, urine analysis, vital signs and ECG parameters.</measure>
    <time_frame>40 weeks including a screening and eligibility assessment phase (4 weeks duration), a 24- week treatment phase, and 12- week post treatment follow up phase.</time_frame>
    <description>Safety and tolerability are assessed by: the nature, severity and frequency of the adverse effects and absolute values and changes over time from pre-dose values for hematology clinical chemistry, urine analysis, vital signs and ECG parameters. Clinical adverse events will be displayed by body system (SOC) for each study subject and by treatment group, using MedDRA coding. Absolute laboratory values, changes and its graded abnormalities will be displayed) for each study subject and by treatment group. The proportions of subjects experiencing Clinical adverse events and laboratory abnormalities of a given type will be computed and presented along with descriptive statistics. Vital signs data will be similarly assessed, and any post baseline changes in physical examination findings will be summarized in tubular form, by subject and by treatment cohort.&#xD;
Summary statistics of efficacy and safety end points will be displayed by stratification parameters</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">41</enrollment>
  <condition>Pharmacological Action</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 patients will be randomly assigned into arm 1; treated for fixed 24 duration with Gratisovir (Sofosbuvir) and Ribavirin. First intervention 'Sofosbuvir oral product' 200 mg tablet with food on daily doses based on body weight (20-29.9 kg will take one 200 mg tab daily); (30-39.9 kg will take 1.5 tab 200 mg daily); (&gt; 40 kg will take 2 tab 200 mg daily).&#xD;
Second intervention 'Ribavirin oral product' 200 mg tab on (15 mg/kg daily) doses based on body weight.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 patients will be randomly assigned into arm 2; treated as response guided duration; patient who show very rapid virological (undetectable HCV RNA after 2 weeks) will be treated for 16 weeks duration and reset will complete the 24 weeks duration.&#xD;
Intervention 'Sofosbuvir Oral Product' 200 mg tablet with food on daily doses based on body weight (20-29.9 kg will take one 200 mg tab daily); (30-39.9 kg will take 1.5 tab 200 mg daily); (&gt; 40 kg will take 2 tab 200 mg daily).&#xD;
Second intervention 'Ribavirin oral product' 200 mg tab on (15 mg/kg daily) doses based on body weight.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sofosbuvir Oral Product</intervention_name>
    <description>direct acting antiviral drug for HCV infection</description>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_label>Arm 2</arm_group_label>
    <other_name>Gratisovir</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ribavirin</intervention_name>
    <description>antiviral drug for HCV infection</description>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_label>Arm 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Male or female child ≥ 10 years and ≤ 18 years of age chronically infected with hepatitis C&#xD;
        virus.&#xD;
&#xD;
        willing and able to complete all study visits and procedures. Acceptance from the parents&#xD;
        will be recruited for giving a verbal and written informed consent.&#xD;
&#xD;
        Patient with child,s Pugh class B or C, compensated cirrhosis may be enrolled.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient with cirrhosis with their alpha fetoprotein is more than 100 ng/ml.&#xD;
&#xD;
          2. Patient with coinfection of hepatitis B virus or Human Immunodeficiency Virus will be&#xD;
             excluded.&#xD;
&#xD;
          3. Creatinine clearance &lt; 50 ml/minute.&#xD;
&#xD;
          4. Albumin&lt;3 gm/dl.&#xD;
&#xD;
          5. aspartate aminotransferase or alanine aminotransferase &gt; 10 upper limit of normal.&#xD;
&#xD;
          6. Pregnant and lactating females.&#xD;
&#xD;
          7. Associated morbidity such as uncontrolled diabetes mellitus, schistosomiasis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Behairy Behairy, professor</last_name>
    <role>Study Director</role>
    <affiliation>National Liver Institute, Egypt</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National liver institute</name>
      <address>
        <city>Segin el Kom</city>
        <state>Menofia</state>
        <zip>32714</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 7, 2016</study_first_posted>
  <last_update_submitted>December 16, 2016</last_update_submitted>
  <last_update_submitted_qc>December 16, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 19, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Liver Institute, Egypt</investigator_affiliation>
    <investigator_full_name>Samira Abdel-Wahab Abdel- Aziz</investigator_full_name>
    <investigator_title>lecturer of pediatric hepatology.</investigator_title>
  </responsible_party>
  <keyword>direct acting antiviral drugs, chronic hepatitis C virus infection</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ribavirin</mesh_term>
    <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/NCT02985281
org study id: 00114/2016
nct id: NCT02985281
lead sponsor: 
collaborator: 
has dmc: Yes
Evaluation of Safety and Efficacy of Gratisovir (Sofosbuvir)- Ribavirin Therapy in Egyptian
      Pediatric Patients With Chronic Hepatitis C Infection aged 10- 18 years old.
Male or female child ≥ 10 years and ≤ 18 years of age chronically infected with hepatitis C
      virus, willing and able to complete all study visits and procedures. Acceptance from the
      parents will be recruited for giving a verbal and written informed consent. Patient with
      childs Pugh class B or C, compensated cirrhosis may be enrolled. Patient with cirrhosis with
      their alpha fetoprotein is more than 100 ng/ml and patient with coinfection of Hepatitis B
      virus or HIV will be excluded. Participation in the study procedures is anticipated to last
      up to 40 weeks including a screening and eligibility assessment phase (4 weeks duration), a
      24- week treatment phase, and 12- week post treatment follow up phase.

      A detailed treatment log of the returned investigational product will be established with the
      investigator (or the pharmacist) and countersigned by the investigator and the monitoring
      team.

      Compliance is assessed by counting the number of returned tablets at each visit.

      A discontinuation is defined as a period with at least seven consecutive days without study
      drug intake.

      Safety and efficacy will be compared between cirrhotic versus non-cirrhotic subjects in
      multivariate model to test the impact of this pretreatment characteristic on safety,
      tolerability and efficacy endpoints.

      Safety analysis:clinical adverse events will be displayed by body system (soc) for each study
      subject and by treatment group, using MedDRA coding. Summary of statistics of safety and
      efficacy endpoints will be displayed by stratification parameters.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of SVR12 in both treatment groups after 12 following completion of treatment (SVR12)
time frame: 40 weeks including a screening and eligibility assessment phase (4 weeks duration), a 24- week treatment phase, and 12- week post treatment follow up phase.
description: incidence of SVR12 in both treatment groups after 12 weeks following completion of treatment (SVR12)
measure: assessment of the nature, severity and frequency of the adverse effects and absolute values and changes over time from pre-dose values for hematology clinical chemistry, urine analysis, vital signs and ECG parameters.
time frame: 40 weeks including a screening and eligibility assessment phase (4 weeks duration), a 24- week treatment phase, and 12- week post treatment follow up phase.
description: Safety and tolerability are assessed by: the nature, severity and frequency of the adverse effects and absolute values and changes over time from pre-dose values for hematology clinical chemistry, urine analysis, vital signs and ECG parameters. Clinical adverse events will be displayed by body system (SOC) for each study subject and by treatment group, using MedDRA coding. Absolute laboratory values, changes and its graded abnormalities will be displayed) for each study subject and by treatment group. The proportions of subjects experiencing Clinical adverse events and laboratory abnormalities of a given type will be computed and presented along with descriptive statistics. Vital signs data will be similarly assessed, and any post baseline changes in physical examination findings will be summarized in tubular form, by subject and by treatment cohort.
Summary statistics of efficacy and safety end points will be displayed by stratification parameters
arm group label: Arm 1
arm group type: Active Comparator
description: 20 patients will be randomly assigned into arm 1; treated for fixed 24 duration with Gratisovir (Sofosbuvir) and Ribavirin. First intervention 'Sofosbuvir oral product' 200 mg tablet with food on daily doses based on body weight (20-29.9 kg will take one 200 mg tab daily); (30-39.9 kg will take 1.5 tab 200 mg daily); (> 40 kg will take 2 tab 200 mg daily).
Second intervention 'Ribavirin oral product' 200 mg tab on (15 mg/kg daily) doses based on body weight.
arm group label: Arm 2
arm group type: Active Comparator
description: 20 patients will be randomly assigned into arm 2; treated as response guided duration; patient who show very rapid virological (undetectable HCV RNA after 2 weeks) will be treated for 16 weeks duration and reset will complete the 24 weeks duration.
Intervention 'Sofosbuvir Oral Product' 200 mg tablet with food on daily doses based on body weight (20-29.9 kg will take one 200 mg tab daily); (30-39.9 kg will take 1.5 tab 200 mg daily); (> 40 kg will take 2 tab 200 mg daily).
Second intervention 'Ribavirin oral product' 200 mg tab on (15 mg/kg daily) doses based on body weight.
intervention type: Drug
intervention name: Sofosbuvir Oral Product
description: direct acting antiviral drug for HCV infection
arm group label: Arm 1
arm group label: Arm 2
other name: Gratisovir
intervention type: Drug
intervention name: Ribavirin
description: antiviral drug for HCV infection
arm group label: Arm 1
arm group label: Arm 2
criteria: 
gender: All
minimum age: 10 Years
maximum age: 18 Years
healthy volunteers: No
last name: Behairy Behairy, professor
role: Study Director
affiliation: National Liver Institute, Egypt
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: National Liver Institute, Egypt
investigator full name: Samira Abdel-Wahab Abdel- Aziz
investigator title: lecturer of pediatric hepatology.
mesh term: Ribavirin
mesh term: Sofosbuvir
sharing ipd: No