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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV Infection
• Intervention / Treatment: Drug: dolutegravir (DTG)/emtricitabine (FTC)/tenofovir alafenamide (TAF) regimen

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alessandra Nardone; Phone Number: +39 049 716 9822; Email: alessandra.nardone@pentafoundation.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy endpoints	- Viral load (VL) <400 c/ml at 24 weeks	From enrollment to the end of treatment at 24 weeks
Efficacy endpoints	Occurrence of new or recurrent WHO clinical stage 3 or 4 event	From enrollment to the end of treatment at 24 weeks

Collaborators and Investigators

• Sponsor: PENTA Foundation
• Collaborators: Radboud University Medical Center; Baylor College of Medicine; Clinton Health Access Initiative Inc.; AMS-PHPT Research Collaboration; University of Zimbabwe Clinical Research Centre (UZCRC)

Study record dates

Study Major Dates

• Study Start (Estimated): January 31, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 1, 2023
• First Submitted That Met QC Criteria: August 8, 2023
• First Posted (Actual): August 15, 2023

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Tenofovir; Emtricitabine; Dolutegravir
• Other Study ID Numbers: UNIVERSAL1; RIA2019PD-2882 (Other Grant/Funding Number: EDCTP2)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will be supporting a generic company dossier subject to FDA evaluation

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No