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UNIVERSAL 1: Pharmacokinetic Study of a Novel DTG/FTC/TAF Dose Ratio for Children (UNIVERSAL1)

Primary Purpose

HIV Infection

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen
Sponsored by
PENTA Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infection

Eligibility Criteria

28 Days - 10 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age between 28 days and 10 years old Weighing 3 to <25 kg Confirmed HIV-1 infection (local, molecular methods) A parent or legal guardian is willing and able to give informed consent on behalf of the child as per national legislation and willing to adhere to the protocol Participant is willing to give informed assent if the trial site clinician deems them old enough and able to understand the age-appropriate information about participation in the study Girls who have reached menarche must have a negative pregnancy test at screening Subject is willing to start DTG/FTC/TAF regimen in the novel dose ratio for HIV treatment Subjects already on a DTG-based ART regimen should be virologically suppressed at screening Exclusion Criteria: Age between 28 days and 10 years old Weighing 3 to <25 kg Confirmed HIV-1 infection (local, molecular methods) A parent or legal guardian is willing and able to give informed consent on behalf of the child as per national legislation and willing to adhere to the protocol Participant is willing to give informed assent if the trial site clinician deems them old enough and able to understand the age-appropriate information about participation in the study Girls who have reached menarche must have a negative pregnancy test at screening Subject is willing to start DTG/FTC/TAF regimen in the novel dose ratio for HIV treatment Subjects already on a DTG-based ART regimen should be virologically suppressed at screening History or presence of known allergy to DTG, FTC or TAF Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), OR ALT ≥3xULN AND bilirubin ≥2xULN Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) Current or anticipated need for TB therapy during the study Use of rifampicin-based therapy within 4 weeks before start trial Presence of comedication known to interact with trial medications Known resistance to INSTI or NRTI

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen

    Arm Description

    Switch or start dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen with a novel dose ratio for HIV treatment

    Outcomes

    Primary Outcome Measures

    Primary endpoints for DTG:
    - Geometric mean Ctrough concentration
    Primary endpoints for DTG:
    Percentage of individual Ctrough concentrations below the 90% effective concentration (EC90) (0.32 mg/L)
    Primary endpoints for DTG:
    - Geometric mean DTG Ctrough, Cmax, and AUC
    Primary safety endpoints
    - Occurrence of serious adverse events
    Primary safety endpoints
    - Occurrence of new clinical and laboratory grade 3 and 4 adverse events
    Primary safety endpoints
    Occurrence of adverse events (of any grade) leading to treatment modification
    Primary endpoints for FTC/TAF:
    - Geometric mean Ctrough, Cmax, and AUC
    Primary endpoints for FTC/TAF:
    Intracellular tenofovir diphosphate (TDP) levels at 24 hours acquired through dried blood spot analysis

    Secondary Outcome Measures

    Efficacy endpoints
    - Viral load (VL) <400 c/ml at 24 weeks
    Efficacy endpoints
    Occurrence of new or recurrent WHO clinical stage 3 or 4 event

    Full Information

    First Posted
    August 1, 2023
    Last Updated
    August 8, 2023
    Sponsor
    PENTA Foundation
    Collaborators
    Radboud University Medical Center, AMS-PHPT Research Collaboration, Baylor College of Medicine, University of Zimbabwe Clinical Research Centre (UZCRC), Clinton Health Access Initiative Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05993767
    Brief Title
    UNIVERSAL 1: Pharmacokinetic Study of a Novel DTG/FTC/TAF Dose Ratio for Children
    Acronym
    UNIVERSAL1
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 31, 2024 (Anticipated)
    Primary Completion Date
    June 30, 2025 (Anticipated)
    Study Completion Date
    December 31, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    PENTA Foundation
    Collaborators
    Radboud University Medical Center, AMS-PHPT Research Collaboration, Baylor College of Medicine, University of Zimbabwe Clinical Research Centre (UZCRC), Clinton Health Access Initiative Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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.
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    HIV Infection

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Model Description
    An interventional, phase I/II, multicenter, single-arm study
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen
    Arm Type
    Experimental
    Arm 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(s)
    dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen
    Intervention Description
    Switch or start dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen with a novel dose ratio for HIV treatment
    Primary Outcome Measure Information:
    Title
    Primary endpoints for DTG:
    Description
    - Geometric mean Ctrough concentration
    Time Frame
    From enrollment to the end of treatment at 24 weeks
    Title
    Primary endpoints for DTG:
    Description
    Percentage of individual Ctrough concentrations below the 90% effective concentration (EC90) (0.32 mg/L)
    Time Frame
    From enrollment to the end of treatment at 24 weeks
    Title
    Primary endpoints for DTG:
    Description
    - Geometric mean DTG Ctrough, Cmax, and AUC
    Time Frame
    From enrollment to the end of treatment at 24 weeks
    Title
    Primary safety endpoints
    Description
    - Occurrence of serious adverse events
    Time Frame
    From enrollment to the end of treatment at 24 weeks
    Title
    Primary safety endpoints
    Description
    - Occurrence of new clinical and laboratory grade 3 and 4 adverse events
    Time Frame
    From enrollment to the end of treatment at 24 weeks
    Title
    Primary safety endpoints
    Description
    Occurrence of adverse events (of any grade) leading to treatment modification
    Time Frame
    From enrollment to the end of treatment at 24 weeks
    Title
    Primary endpoints for FTC/TAF:
    Description
    - Geometric mean Ctrough, Cmax, and AUC
    Time Frame
    From enrollment to the end of treatment at 24 weeks
    Title
    Primary endpoints for FTC/TAF:
    Description
    Intracellular tenofovir diphosphate (TDP) levels at 24 hours acquired through dried blood spot analysis
    Time Frame
    From enrollment to the end of treatment at 24 weeks
    Secondary Outcome Measure Information:
    Title
    Efficacy endpoints
    Description
    - Viral load (VL) <400 c/ml at 24 weeks
    Time Frame
    From enrollment to the end of treatment at 24 weeks
    Title
    Efficacy endpoints
    Description
    Occurrence of new or recurrent WHO clinical stage 3 or 4 event
    Time Frame
    From enrollment to the end of treatment at 24 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    28 Days
    Maximum Age & Unit of Time
    10 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age between 28 days and 10 years old Weighing 3 to <25 kg Confirmed HIV-1 infection (local, molecular methods) A parent or legal guardian is willing and able to give informed consent on behalf of the child as per national legislation and willing to adhere to the protocol Participant is willing to give informed assent if the trial site clinician deems them old enough and able to understand the age-appropriate information about participation in the study Girls who have reached menarche must have a negative pregnancy test at screening Subject is willing to start DTG/FTC/TAF regimen in the novel dose ratio for HIV treatment Subjects already on a DTG-based ART regimen should be virologically suppressed at screening Exclusion Criteria: Age between 28 days and 10 years old Weighing 3 to <25 kg Confirmed HIV-1 infection (local, molecular methods) A parent or legal guardian is willing and able to give informed consent on behalf of the child as per national legislation and willing to adhere to the protocol Participant is willing to give informed assent if the trial site clinician deems them old enough and able to understand the age-appropriate information about participation in the study Girls who have reached menarche must have a negative pregnancy test at screening Subject is willing to start DTG/FTC/TAF regimen in the novel dose ratio for HIV treatment Subjects already on a DTG-based ART regimen should be virologically suppressed at screening History or presence of known allergy to DTG, FTC or TAF Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), OR ALT ≥3xULN AND bilirubin ≥2xULN Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) Current or anticipated need for TB therapy during the study Use of rifampicin-based therapy within 4 weeks before start trial Presence of comedication known to interact with trial medications Known resistance to INSTI or NRTI
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Alessandra Nardone
    Phone
    +39 049 716 9822
    Email
    alessandra.nardone@pentafoundation.org

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    IPD will be supporting a generic company dossier subject to FDA evaluation

    Learn more about this trial

    UNIVERSAL 1: Pharmacokinetic Study of a Novel DTG/FTC/TAF Dose Ratio for Children

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