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

PENTA Foundation

Status and phase: Enrolling; Phase 2

Conditions: HIV Infection

Treatments: Drug: dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen; Drug: Dolutegravir (DTG)/ Emtricitabine (FTC)/tenofovir alafenamide (TAF)

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT05993767

UNIVERSAL1

RIA2019PD-2882 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 28 days to 10 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

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

Experimental group

Description:

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

Treatment:

Drug: Dolutegravir (DTG)/ Emtricitabine (FTC)/tenofovir alafenamide (TAF)

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