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/NCT05993767</url>
    </required_header>
    <id_info>
      <org_study_id>UNIVERSAL1</org_study_id>
      <secondary_id>RIA2019PD-2882</secondary_id>
      <nct_id>NCT05993767</nct_id>
    </id_info>
    <brief_title>UNIVERSAL 1: Pharmacokinetic Study of a Novel DTG/FTC/TAF Dose Ratio for Children</brief_title>
    <acronym>UNIVERSAL1</acronym>
    <official_title>Pharmacokinetic Study of an Optimized Dose Ratio of Dolutegravir/Emtricitabine/Tenofovir Alafenamide Fumarate: Expediting a UNIVERSAL First Line Regimen for All Children Living With HIV in Africa</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>PENTA Foundation</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Radboud University Medical Center</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>AMS-PHPT Research Collaboration</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Baylor College of Medicine</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>University of Zimbabwe Clinical Research Centre (UZCRC)</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Clinton Health Access Initiative Inc.</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>PENTA Foundation</source>
    <oversight_info>
      <has_dmc>Yes</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>
        This study aims to find out whether treating children living with HIV with three anti-HIV&#xD;
        medicines, dolutegravir (DTG), emtricitabine (FTC) and tenofovir alafenamide (TAF), with a&#xD;
        novel dose ratio will achieve adequate drug concentrations and is safe. The optimal&#xD;
        DTG/FTC/TAF dose ratio will be used for the development of a fixed-dose combination&#xD;
        dispersible tablet.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Dolutegravir (DTG), Emtricitabine (FTC) and Tenofovir alafenamide (TAF) are anti-HIV&#xD;
        medicines. DTG works very well, can be taken once-daily and has few side effects. In&#xD;
        international treatment guidelines, DTG is one of the most recommended medicines for adults&#xD;
        and young people. Emtricitabine is also one of the preferred medicines in anti-HIV treatment&#xD;
        for adults and children. Tenofovir alafenamide (TAF) is not yet recommended in children &lt;25&#xD;
        kg, however TAF could potentially be used safely and effectively in children.&#xD;
  &#xD;
        Combining DTG, FTC and TAF in a specific dose ratio may offer treatment that is safe and&#xD;
        effective. If so, a combination dispersible tablet containing these three medicines can be&#xD;
        developed and this will allow the same HIV medicines to be used across children and adults.&#xD;
  &#xD;
        This study will include 50 children aged 28 days to less than 10 years old who are living&#xD;
        with HIV. All participants will receive the same treatment with DTG, FTC and TAF. Depending&#xD;
        on their weight, participants will receive a certain number of tablets that can be dispersed&#xD;
        and taken once a day. All children in the study will have clinical assessments. Blood tests&#xD;
        will be performed to make sure that the medicines are safe and, at some visits, participants&#xD;
        and carers will also be asked to answer some questions on taking medicine and how medicine&#xD;
        tastes. All children will be followed up for 24 weeks.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 31, 2024</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">June 30, 2025</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>An interventional, phase I/II, multicenter, single-arm study</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Primary endpoints for DTG:</measure>
      <time_frame>From enrollment to the end of treatment at 24 weeks</time_frame>
      <description>- Geometric mean Ctrough concentration</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Primary endpoints for DTG:</measure>
      <time_frame>From enrollment to the end of treatment at 24 weeks</time_frame>
      <description>Percentage of individual Ctrough concentrations below the 90% effective concentration (EC90) (0.32 mg/L)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Primary endpoints for DTG:</measure>
      <time_frame>From enrollment to the end of treatment at 24 weeks</time_frame>
      <description>- Geometric mean DTG Ctrough, Cmax, and AUC</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Primary safety endpoints</measure>
      <time_frame>From enrollment to the end of treatment at 24 weeks</time_frame>
      <description>- Occurrence of serious adverse events</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Primary safety endpoints</measure>
      <time_frame>From enrollment to the end of treatment at 24 weeks</time_frame>
      <description>- Occurrence of new clinical and laboratory grade 3 and 4 adverse events</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Primary safety endpoints</measure>
      <time_frame>From enrollment to the end of treatment at 24 weeks</time_frame>
      <description>Occurrence of adverse events (of any grade) leading to treatment modification</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Primary endpoints for FTC/TAF:</measure>
      <time_frame>From enrollment to the end of treatment at 24 weeks</time_frame>
      <description>- Geometric mean Ctrough, Cmax, and AUC</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Primary endpoints for FTC/TAF:</measure>
      <time_frame>From enrollment to the end of treatment at 24 weeks</time_frame>
      <description>Intracellular tenofovir diphosphate (TDP) levels at 24 hours acquired through dried blood spot analysis</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Efficacy endpoints</measure>
      <time_frame>From enrollment to the end of treatment at 24 weeks</time_frame>
      <description>- Viral load (VL) &lt;400 c/ml at 24 weeks</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy endpoints</measure>
      <time_frame>From enrollment to the end of treatment at 24 weeks</time_frame>
      <description>Occurrence of new or recurrent WHO clinical stage 3 or 4 event</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>HIV Infection</condition>
    <arm_group>
      <arm_group_label>dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Switch or start dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen with a novel dose ratio for HIV treatment</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen</intervention_name>
      <description>Switch or start dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen with a novel dose ratio for HIV treatment</description>
      <arm_group_label>dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age between 28 days and 10 years old&#xD;
  &#xD;
            -  Weighing 3 to &lt;25 kg&#xD;
  &#xD;
            -  Confirmed HIV-1 infection (local, molecular methods)&#xD;
  &#xD;
            -  A parent or legal guardian is willing and able to give informed consent on behalf of&#xD;
               the child as per national legislation and willing to adhere to the protocol&#xD;
  &#xD;
            -  Participant is willing to give informed assent if the trial site clinician deems them&#xD;
               old enough and able to understand the age-appropriate information about participation&#xD;
               in the study&#xD;
  &#xD;
            -  Girls who have reached menarche must have a negative pregnancy test at screening&#xD;
  &#xD;
            -  Subject is willing to start DTG/FTC/TAF regimen in the novel dose ratio for HIV&#xD;
               treatment&#xD;
  &#xD;
            -  Subjects already on a DTG-based ART regimen should be virologically suppressed at&#xD;
               screening&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Age between 28 days and 10 years old&#xD;
  &#xD;
            -  Weighing 3 to &lt;25 kg&#xD;
  &#xD;
            -  Confirmed HIV-1 infection (local, molecular methods)&#xD;
  &#xD;
            -  A parent or legal guardian is willing and able to give informed consent on behalf of&#xD;
               the child as per national legislation and willing to adhere to the protocol&#xD;
  &#xD;
            -  Participant is willing to give informed assent if the trial site clinician deems them&#xD;
               old enough and able to understand the age-appropriate information about participation&#xD;
               in the study&#xD;
  &#xD;
            -  Girls who have reached menarche must have a negative pregnancy test at screening&#xD;
  &#xD;
            -  Subject is willing to start DTG/FTC/TAF regimen in the novel dose ratio for HIV&#xD;
               treatment&#xD;
  &#xD;
            -  Subjects already on a DTG-based ART regimen should be virologically suppressed at&#xD;
               screening&#xD;
  &#xD;
            -  History or presence of known allergy to DTG, FTC or TAF&#xD;
  &#xD;
            -  Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), OR ALT ≥3xULN&#xD;
               AND bilirubin ≥2xULN&#xD;
  &#xD;
            -  Patients with severe hepatic impairment or unstable liver disease (as defined by the&#xD;
               presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or&#xD;
               gastric varices, or persistent jaundice), known biliary abnormalities (with the&#xD;
               exception of Gilbert's syndrome or asymptomatic gallstones)&#xD;
  &#xD;
            -  Current or anticipated need for TB therapy during the study&#xD;
  &#xD;
            -  Use of rifampicin-based therapy within 4 weeks before start trial&#xD;
  &#xD;
            -  Presence of comedication known to interact with trial medications&#xD;
  &#xD;
            -  Known resistance to INSTI or NRTI&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>28 Days</minimum_age>
      <maximum_age>10 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Alessandra Nardone</last_name>
      <phone>+39 049 716 9822</phone>
      <email>alessandra.nardone@pentafoundation.org</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 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>HIV Infections</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tenofovir</mesh_term>
      <mesh_term>Emtricitabine</mesh_term>
      <mesh_term>Dolutegravir</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>IPD will be supporting a generic company dossier subject to FDA evaluation</ipd_description>
    </patient_data>
    <!-- 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/NCT05993767
  org study id: UNIVERSAL1
  secondary id: RIA2019PD-2882
  nct id: NCT05993767
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This study aims to find out whether treating children living with HIV with three anti-HIV
        medicines, dolutegravir (DTG), emtricitabine (FTC) and tenofovir alafenamide (TAF), with a
        novel dose ratio will achieve adequate drug concentrations and is safe. The optimal
        DTG/FTC/TAF dose ratio will be used for the development of a fixed-dose combination
        dispersible tablet.
  Dolutegravir (DTG), Emtricitabine (FTC) and Tenofovir alafenamide (TAF) are anti-HIV
        medicines. DTG works very well, can be taken once-daily and has few side effects. In
        international treatment guidelines, DTG is one of the most recommended medicines for adults
        and young people. Emtricitabine is also one of the preferred medicines in anti-HIV treatment
        for adults and children. Tenofovir alafenamide (TAF) is not yet recommended in children <25
        kg, however TAF could potentially be used safely and effectively in children.
  
        Combining DTG, FTC and TAF in a specific dose ratio may offer treatment that is safe and
        effective. If so, a combination dispersible tablet containing these three medicines can be
        developed and this will allow the same HIV medicines to be used across children and adults.
  
        This study will include 50 children aged 28 days to less than 10 years old who are living
        with HIV. All participants will receive the same treatment with DTG, FTC and TAF. Depending
        on their weight, participants will receive a certain number of tablets that can be dispersed
        and taken once a day. All children in the study will have clinical assessments. Blood tests
        will be performed to make sure that the medicines are safe and, at some visits, participants
        and carers will also be asked to answer some questions on taking medicine and how medicine
        tastes. All children will be followed up for 24 weeks.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: An interventional, phase I/II, multicenter, single-arm study
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Primary endpoints for DTG:
  time frame: From enrollment to the end of treatment at 24 weeks
  description: - Geometric mean Ctrough concentration
  measure: Primary endpoints for DTG:
  time frame: From enrollment to the end of treatment at 24 weeks
  description: Percentage of individual Ctrough concentrations below the 90% effective concentration (EC90) (0.32 mg/L)
  measure: Primary endpoints for DTG:
  time frame: From enrollment to the end of treatment at 24 weeks
  description: - Geometric mean DTG Ctrough, Cmax, and AUC
  measure: Primary safety endpoints
  time frame: From enrollment to the end of treatment at 24 weeks
  description: - Occurrence of serious adverse events
  measure: Primary safety endpoints
  time frame: From enrollment to the end of treatment at 24 weeks
  description: - Occurrence of new clinical and laboratory grade 3 and 4 adverse events
  measure: Primary safety endpoints
  time frame: From enrollment to the end of treatment at 24 weeks
  description: Occurrence of adverse events (of any grade) leading to treatment modification
  measure: Primary endpoints for FTC/TAF:
  time frame: From enrollment to the end of treatment at 24 weeks
  description: - Geometric mean Ctrough, Cmax, and AUC
  measure: Primary endpoints for FTC/TAF:
  time frame: From enrollment to the end of treatment at 24 weeks
  description: Intracellular tenofovir diphosphate (TDP) levels at 24 hours acquired through dried blood spot analysis
  measure: Efficacy endpoints
  time frame: From enrollment to the end of treatment at 24 weeks
  description: - Viral load (VL) <400 c/ml at 24 weeks
  measure: Efficacy endpoints
  time frame: From enrollment to the end of treatment at 24 weeks
  description: Occurrence of new or recurrent WHO clinical stage 3 or 4 event
  arm group label: dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen
  arm group type: Experimental
  description: Switch or start dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen with a novel dose ratio for HIV treatment
  intervention type: Drug
  intervention name: dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen
  description: Switch or start dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen with a novel dose ratio for HIV treatment
  arm group label: dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen
  criteria: 
  gender: All
  minimum age: 28 Days
  maximum age: 10 Years
  healthy volunteers: No
  last name: Alessandra Nardone
  phone: +39 049 716 9822
  email: alessandra.nardone@pentafoundation.org
  responsible party type: Sponsor
  mesh term: HIV Infections
  mesh term: Tenofovir
  mesh term: Emtricitabine
  mesh term: Dolutegravir
  sharing ipd: No
  ipd description: IPD will be supporting a generic company dossier subject to FDA evaluation