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
Overview
- Phase
- Phase 2
- Intervention
- dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen
- Conditions
- HIV Infection
- Sponsor
- PENTA Foundation
- Enrollment
- 53
- Locations
- 3
- Primary Endpoint
- Primary endpoints for DTG:
- Status
- Completed
- Last Updated
- last month
Overview
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. Subjects will receive DTG 10 mg dispersible tablets and FTC/TAF 15/1.88 mg dispersible tablets or DTG 50 mg film coated tablets and FTC/TAF 200/25 mg film coated tablets depending on weight band. 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.
Investigators
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
Arms & Interventions
dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen
Switch or start dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen with a novel dose ratio for HIV treatment. Subjects will receive DTG 10 mg dispersible tablets and FTC/TAF 15/1.88 mg dispersible tablets or DTG 50 mg film coated tablets and FTC/TAF 200/25 mg film coated tablets depending on weight band
Intervention: dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen
dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen
Switch or start dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen with a novel dose ratio for HIV treatment. Subjects will receive DTG 10 mg dispersible tablets and FTC/TAF 15/1.88 mg dispersible tablets or DTG 50 mg film coated tablets and FTC/TAF 200/25 mg film coated tablets depending on weight band
Intervention: Dolutegravir (DTG)/ Emtricitabine (FTC)/tenofovir alafenamide (TAF)
Outcomes
Primary Outcomes
Primary endpoints for DTG:
Time Frame: From enrollment to the end of treatment at 24 weeks
\- Geometric mean DTG Ctrough, Cmax, and AUC
Primary safety endpoints
Time Frame: From enrollment to the end of treatment at 24 weeks
Occurrence of adverse events (of any grade) leading to treatment modification
Primary endpoints for FTC/TAF:
Time Frame: From enrollment to the end of treatment at 24 weeks
Intracellular tenofovir diphosphate (TDP) levels at 24 hours acquired through dried blood spot analysis
Secondary Outcomes
- Efficacy endpoints(From enrollment to the end of treatment at 24 weeks)