xml: <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/NCT05992077</url>
    </required_header>
    <id_info>
      <org_study_id>ANRS 12420 HEPEDIAC</org_study_id>
      <nct_id>NCT05992077</nct_id>
    </id_info>
    <brief_title>Study of DAA Treatment for Children and Adolescents With Active HCV Infection in Cambodia</brief_title>
    <acronym>HEPEDIAC</acronym>
    <official_title>Pilot Therapeutic Study of DAA Treatment for Children and Adolescents With Active HCV Infection in Cambodia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>ANRS, Emerging Infectious Diseases</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>ANRS, Emerging Infectious Diseases</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this clinical trial is to evaluate the effectiveness of sofosbuvir/daclatasvir&#xD;
        combination for children aged ≥ 6 years old and adolescents with active HCV infection in&#xD;
        Cambodia&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Non-comparative multicenter pilot therapeutic prospective study conducted in Phnom Penh and&#xD;
        Siem Reap and divided in 2 phases:&#xD;
  &#xD;
        Screening phase:&#xD;
  &#xD;
        First, all children aged more than 6 years old and adolescents under 18 years old will be&#xD;
        screened for HCV infection using Bioline HCV rapid test in two paediatric populations in&#xD;
        Phnom Penh and Siem Reap: 1/ children born from HIV/HCV co-infected women followed in OI/ART&#xD;
        sites 2/ children hospitalized in paediatric department of Kantha Bopha Foundation Children's&#xD;
        Hospitals and of the National Pediatric Hospital.&#xD;
  &#xD;
        HCV RNA will be performed in case of HCV rapid test positivity. A case-control study will be&#xD;
        performed to evaluate the risk factors associated to HCV acquisition. Cases will be defined&#xD;
        as children with positive HCV RDT and controls as children with negative HCV RDT. Four&#xD;
        controls will be randomly selected for one case.&#xD;
  &#xD;
        Therapeutic phase:&#xD;
  &#xD;
        Children and adolescents confirmed with active HCV infection (positive HCV RNA) during the&#xD;
        first phase will be referred to a specific consultation in Kantha Bopha hospital or National&#xD;
        Pediatric Hospital for treatment after evaluation of liver disease. Patients with a weight &gt;&#xD;
        25 kg will be treated with a sofosbuvir/daclatasvir combination for 12 weeks with adult dose&#xD;
        (400/60 mg), children with a weight between 14 and 25 kg will be treated with the same&#xD;
        sofosbuvir/daclatasvir combination with the half adult dose (200/30 mg) for 12 weeks. For all&#xD;
        children and adolescents, residual plasma concentrations (trough concentrations) of the drugs&#xD;
        will be assessed after 2 weeks of treatment. For the first 20 children and adolescents&#xD;
        included (10 children weighing between 14 and 25 kg and 10 weighing more than 25 kg),&#xD;
        whatever their HIV status and ARV treatment, a complete pharmacokinetic analysis will be&#xD;
        performed prior to drug administration and +1h, +2h, +6h and +10h after drugs intake. A&#xD;
        non-compartimental analysis using Phoenix WinNonlin 8.1 (Certara, Princeton, NJ, USA) will be&#xD;
        performed to estimate the pharmacokinetic parameters of sofosbuvir, GS-331007 and&#xD;
        daclatasvir. Maximal concentration (Cmax), trough concentration at steady state (Ct), minimal&#xD;
        concentration (Cmin) and the time required to reach Cmax (Tmax) are the observed parameters.&#xD;
        The area under the curve (AUCtau) will be estimated by the linear up log down trapezoidal&#xD;
        method using the predose concentration as 24-hour postdose concentrations.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 7, 2023</start_date>
    <completion_date type="Anticipated">June 2025</completion_date>
    <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
    <phase>N/A</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>Non-comparative multicenter pilot therapeutic prospective study. First, all children aged ≥ 6 years old and adolescents will be screened for HCV infection using HCV rapid test. HCV RNA will be performed in case of HCV rapid test positivity. Then, children and adolescents confirmed with active HCV infection (positive HCV RNA) during the screening phase will be referred to a specific consultation for treatment after evaluation of liver disease.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Evaluation of the effectiveness of sofosbuvir/daclatasvir combination for children aged ≥ 6 years old and adolescents with active HCV infection in Cambodia</measure>
      <time_frame>24 months</time_frame>
      <description>The proportion of patients with sustained virologic response defined by HCV RNA below the lower limit of quantification range of the viral load (undetectable viral load) 12 weeks after discontinuation of study drugs (SVR12). Detectable HCV RNA at the SVR12 study visit, permanent discontinuation of DAA, death, discontinuation of the study (loss to follow-up, transfer-out) will be considered as failures.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Evaluation of the liver-related events</measure>
      <time_frame>24 months</time_frame>
      <description>Proportion of patients with symptomatic cirrhosis and evaluation of Child-Pugh score&#xD;
  Proportion of patients with APRI (AST to Platelet Index Ratio) score &gt; 2 and/or FIB-4 (Fibrosis-4) score &gt; 3.25&#xD;
  Proportion of patients with liver elasticity &gt; 9 kPa&#xD;
  Proportion of patients with hepato-cellular carcinoma</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Occurrence of grade 3-4 adverse events (ANRS grading table);</measure>
      <time_frame>24 months</time_frame>
      <description>Frequency, type and time to grade 3 or 4 adverse clinical or biological events. All adverse events will be graded according to the Division of AIDS ( DAIDS) grading table;&#xD;
  Frequency, type and time to drug-related clinical or biological adverse reactions of grade 3 or 4 or leading to treatment interruption</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adherence</measure>
      <time_frame>24 months</time_frame>
      <description>The adherence to DAA treatment will be assessed by accountability (drug pill count)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximal Plasma Concentration (Cmax) of DAA</measure>
      <time_frame>24 months</time_frame>
      <description>Cmax of Sofosbuvir, GS-331007 and Daclatasvir measured in plasma samples</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration versus time curve over the dosing interval (AUCtau) of DAA</measure>
      <time_frame>24 months</time_frame>
      <description>AUCtau of Sofosbuvir, GS-331007 and Daclatasvir will be estimated by the linear up log down trapezoidal method</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Risk factors of HCV acquisition through questionnaire</measure>
      <time_frame>24 months</time_frame>
      <description>Case-control study to evaluate the risk factors associated to HCV acquisition. The questionnaire include information on family disease history, medical care received (injections, blood transfusion, surgery), dental care, tatoos, injecting drug user, use of traditional medicine, and sharing of hygiene tools.</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">36600</enrollment>
    <condition>HCV Infection</condition>
    <arm_group>
      <arm_group_label>Therapeutic phase</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Children and adolescents confirmed with active HCV infection (positive HCV RNA) during the screening phase will be referred to a specific consultation in Kantha Bopha hospital and in the National Pediatric Hospital for treatment after evaluation of liver disease. Patients with a weight &gt; 25 kg will be treated with a sofosbuvir/daclatasvir combination for 12 weeks with adult dose (400/60 mg), children with a weight between 14 and 25 kg will be treated with the same sofosbuvir/daclatasvir combination with the half adult dose (200/30 mg) for 12 weeks. For all children and adolescents, residual plasma concentrations (trough concentrations) of the drugs will be assessed after 2 weeks of treatment.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Sofosbuvir/Daclatasvir</intervention_name>
      <description>Patients with a weight &gt; 25 kg will be treated with a sofosbuvir/daclatasvir combination for 12 weeks with adult dose (400/60 mg), children with a weight between 14 and 25 kg will be treated with the same sofosbuvir/daclatasvir combination with the half adult dose (200/30 mg) for 12 weeks.</description>
      <arm_group_label>Therapeutic phase</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Screening phase Inclusion criteria&#xD;
  &#xD;
            -  Aged ≥ 6 years old with weight ≥ 14 kg&#xD;
  &#xD;
            -  Aged &lt;18 years old&#xD;
  &#xD;
            -  Hospitalized in one of the 3 paediatric departments of Kantha Bopha hospitals in Phnom&#xD;
               Penh, Jayavarman VII hospital in Siem Reap OR in the pediatric department of the&#xD;
               National Pediatric hospital OR born from HIV/HCV co-infected women followed in OI/ART&#xD;
               sites in Phnom Penh&#xD;
  &#xD;
            -  Informed consent obtained with information sheet given and explained before the&#xD;
               inclusion visit, the consent form signed by at least one of the 2 parents or legal&#xD;
               guardians and oral assent collected if the child ≥ 13 years old, at the latest the day&#xD;
               of the inclusion&#xD;
  &#xD;
          Non-inclusion criteria&#xD;
  &#xD;
          - Any medical condition requiring intensive care and/or acute surgery&#xD;
  &#xD;
          Therapeutic phase Inclusion criteria&#xD;
  &#xD;
            -  Aged ≥ 6 years old with weight ≥ 14 kg&#xD;
  &#xD;
            -  Aged &lt; 18 years old&#xD;
  &#xD;
            -  HCV RNA detectable&#xD;
  &#xD;
            -  HCV treatment naive&#xD;
  &#xD;
            -  In case of HIV coinfection,&#xD;
  &#xD;
                 -  HIV-1 infection confirmed according to Cambodian screening policies&#xD;
  &#xD;
                 -  On ART for more than 6 months&#xD;
  &#xD;
                 -  CD4 cell-count&gt; 100 cells/μL and &gt; 15% and HIV viral load &lt; 1000 copies/mL at&#xD;
                    inclusion visit&#xD;
  &#xD;
            -  Informed consent obtained with information sheet given and explained before the&#xD;
               inclusion visit and the consent form signed by at least one of the 2 parents and oral&#xD;
               assent collected if the child ≥ 13 years old, before any sample or drug administration&#xD;
               corresponding to the therapeutic phase.&#xD;
  &#xD;
          Non-inclusion Criteria:&#xD;
  &#xD;
            -  Suspicion of evidence of hepato-cellular carcinoma (HCC) or any other neoplasia&#xD;
  &#xD;
            -  Decompensated cirrhosis&#xD;
  &#xD;
            -  Co-infection with HBV (positive HBsAg)&#xD;
  &#xD;
            -  Advanced/terminal renal disease defined as serum creatinine clearance &lt; 30 mL/min&#xD;
  &#xD;
            -  Active tuberculosis under treatment&#xD;
  &#xD;
            -  In case of HIV coinfection,&#xD;
  &#xD;
                 -  Repeated ART failures and impossibility of prescription of an effective ART&#xD;
                    regimen&#xD;
  &#xD;
                 -  Active opportunistic infection (OI)&#xD;
  &#xD;
            -  Current pregnancy or breast feeding&#xD;
  &#xD;
            -  Use of any drug known to interact with Sofosbuvir or Daclatasvir and for which&#xD;
               temporary cessation or dose modification would be impossible&#xD;
  &#xD;
            -  Any concomitant medical condition that, according to the clinical site investigator,&#xD;
               would contraindicate participation in the study&#xD;
  &#xD;
            -  Concurrent participation in any other clinical trial without written agreement of the&#xD;
               two study investigators&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>6 Years</minimum_age>
      <maximum_age>17 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Fatoumata Coulibaly</last_name>
      <phone>0144236110</phone>
      <phone_ext>+33</phone_ext>
      <email>fatoumata.coulibaly@anrs.fr</email>
    </overall_contact>
    <location>
      <facility>
        <name>Clinical Trial Unit (Ctu)</name>
        <address>
          <city>Phnom Penh</city>
          <zip>BP 983</zip>
          <country>Cambodia</country>
        </address>
      </facility>
      <contact>
        <last_name>Nathalie DE REKENEIRE, Dr</last_name>
        <email>nderekeneire@pasteur-kh.org</email>
      </contact>
      <investigator>
        <last_name>Vichea OUK, Dr</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Olivier SEGERAL, Dr</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Cambodia</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Infections</mesh_term>
      <mesh_term>Communicable Diseases</mesh_term>
      <mesh_term>Hepatitis C</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Sofosbuvir</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05992077
  org study id: ANRS 12420 HEPEDIAC
  nct id: NCT05992077
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical trial is to evaluate the effectiveness of sofosbuvir/daclatasvir
        combination for children aged ≥ 6 years old and adolescents with active HCV infection in
        Cambodia
  Non-comparative multicenter pilot therapeutic prospective study conducted in Phnom Penh and
        Siem Reap and divided in 2 phases:
  
        Screening phase:
  
        First, all children aged more than 6 years old and adolescents under 18 years old will be
        screened for HCV infection using Bioline HCV rapid test in two paediatric populations in
        Phnom Penh and Siem Reap: 1/ children born from HIV/HCV co-infected women followed in OI/ART
        sites 2/ children hospitalized in paediatric department of Kantha Bopha Foundation Children's
        Hospitals and of the National Pediatric Hospital.
  
        HCV RNA will be performed in case of HCV rapid test positivity. A case-control study will be
        performed to evaluate the risk factors associated to HCV acquisition. Cases will be defined
        as children with positive HCV RDT and controls as children with negative HCV RDT. Four
        controls will be randomly selected for one case.
  
        Therapeutic phase:
  
        Children and adolescents confirmed with active HCV infection (positive HCV RNA) during the
        first phase will be referred to a specific consultation in Kantha Bopha hospital or National
        Pediatric Hospital for treatment after evaluation of liver disease. Patients with a weight >
        25 kg will be treated with a sofosbuvir/daclatasvir combination for 12 weeks with adult dose
        (400/60 mg), children with a weight between 14 and 25 kg will be treated with the same
        sofosbuvir/daclatasvir combination with the half adult dose (200/30 mg) for 12 weeks. For all
        children and adolescents, residual plasma concentrations (trough concentrations) of the drugs
        will be assessed after 2 weeks of treatment. For the first 20 children and adolescents
        included (10 children weighing between 14 and 25 kg and 10 weighing more than 25 kg),
        whatever their HIV status and ARV treatment, a complete pharmacokinetic analysis will be
        performed prior to drug administration and +1h, +2h, +6h and +10h after drugs intake. A
        non-compartimental analysis using Phoenix WinNonlin 8.1 (Certara, Princeton, NJ, USA) will be
        performed to estimate the pharmacokinetic parameters of sofosbuvir, GS-331007 and
        daclatasvir. Maximal concentration (Cmax), trough concentration at steady state (Ct), minimal
        concentration (Cmin) and the time required to reach Cmax (Tmax) are the observed parameters.
        The area under the curve (AUCtau) will be estimated by the linear up log down trapezoidal
        method using the predose concentration as 24-hour postdose concentrations.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Non-comparative multicenter pilot therapeutic prospective study. First, all children aged ≥ 6 years old and adolescents will be screened for HCV infection using HCV rapid test. HCV RNA will be performed in case of HCV rapid test positivity. Then, children and adolescents confirmed with active HCV infection (positive HCV RNA) during the screening phase will be referred to a specific consultation for treatment after evaluation of liver disease.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Evaluation of the effectiveness of sofosbuvir/daclatasvir combination for children aged ≥ 6 years old and adolescents with active HCV infection in Cambodia
  time frame: 24 months
  description: The proportion of patients with sustained virologic response defined by HCV RNA below the lower limit of quantification range of the viral load (undetectable viral load) 12 weeks after discontinuation of study drugs (SVR12). Detectable HCV RNA at the SVR12 study visit, permanent discontinuation of DAA, death, discontinuation of the study (loss to follow-up, transfer-out) will be considered as failures.
  measure: Evaluation of the liver-related events
  time frame: 24 months
  description: Proportion of patients with symptomatic cirrhosis and evaluation of Child-Pugh score
  Proportion of patients with APRI (AST to Platelet Index Ratio) score > 2 and/or FIB-4 (Fibrosis-4) score > 3.25
  Proportion of patients with liver elasticity > 9 kPa
  Proportion of patients with hepato-cellular carcinoma
  measure: Occurrence of grade 3-4 adverse events (ANRS grading table);
  time frame: 24 months
  description: Frequency, type and time to grade 3 or 4 adverse clinical or biological events. All adverse events will be graded according to the Division of AIDS ( DAIDS) grading table;
  Frequency, type and time to drug-related clinical or biological adverse reactions of grade 3 or 4 or leading to treatment interruption
  measure: Adherence
  time frame: 24 months
  description: The adherence to DAA treatment will be assessed by accountability (drug pill count)
  measure: Maximal Plasma Concentration (Cmax) of DAA
  time frame: 24 months
  description: Cmax of Sofosbuvir, GS-331007 and Daclatasvir measured in plasma samples
  measure: Area under the plasma concentration versus time curve over the dosing interval (AUCtau) of DAA
  time frame: 24 months
  description: AUCtau of Sofosbuvir, GS-331007 and Daclatasvir will be estimated by the linear up log down trapezoidal method
  measure: Risk factors of HCV acquisition through questionnaire
  time frame: 24 months
  description: Case-control study to evaluate the risk factors associated to HCV acquisition. The questionnaire include information on family disease history, medical care received (injections, blood transfusion, surgery), dental care, tatoos, injecting drug user, use of traditional medicine, and sharing of hygiene tools.
  arm group label: Therapeutic phase
  arm group type: Experimental
  description: Children and adolescents confirmed with active HCV infection (positive HCV RNA) during the screening phase will be referred to a specific consultation in Kantha Bopha hospital and in the National Pediatric Hospital for treatment after evaluation of liver disease. Patients with a weight > 25 kg will be treated with a sofosbuvir/daclatasvir combination for 12 weeks with adult dose (400/60 mg), children with a weight between 14 and 25 kg will be treated with the same sofosbuvir/daclatasvir combination with the half adult dose (200/30 mg) for 12 weeks. For all children and adolescents, residual plasma concentrations (trough concentrations) of the drugs will be assessed after 2 weeks of treatment.
  intervention type: Drug
  intervention name: Sofosbuvir/Daclatasvir
  description: Patients with a weight > 25 kg will be treated with a sofosbuvir/daclatasvir combination for 12 weeks with adult dose (400/60 mg), children with a weight between 14 and 25 kg will be treated with the same sofosbuvir/daclatasvir combination with the half adult dose (200/30 mg) for 12 weeks.
  arm group label: Therapeutic phase
  criteria: 
  gender: All
  minimum age: 6 Years
  maximum age: 17 Years
  healthy volunteers: No
  last name: Fatoumata Coulibaly
  phone: 0144236110
  phone ext: +33
  email: fatoumata.coulibaly@anrs.fr
  facility: 
  contact: 
  investigator: 
  investigator: 
  country: Cambodia
  responsible party type: Sponsor
  mesh term: Infections
  mesh term: Communicable Diseases
  mesh term: Hepatitis C
  mesh term: Sofosbuvir