NCT05780073

Safety and Impact of Dasatinib on Viral Persistence and Inflammation in People With HIV Under Antiretroviral Treatment

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: Fundació Institut Germans Trias i Pujol · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to evaluate the safety, tolerability and Impact of low dose Dasatinib in People with Human Immunodeficiency Virus (PWH) on suppressive Combined Antiretroviral Therapy (cART),. The main question it aims to answer are: * How safe and tolerable is Dasatinib administered at low dose * To evaluate the on-target/biological effect of Dasatinib in "in vitro" T-cells activation and its durability after completion of the treatment * To evaluate the effect of Dasatinib on inflammation and immune activation, on the HIV-1 reservoir, and on cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) cell counts. * To characterize Dasatinib concentrations in plasma and its relationships with the observed effects. Participants will be treated with Dasatinib or matched Placebo once a day for 24 weeks. Suppressive cART will remain unchanged during the entire study. Participants will be followed until week 48, in a total of eleven visits.

Detailed description

This is a Phase II, single-center, randomized, double-blind, placebo-controlled clinical trial in People with Human Immunodeficiency Virus (PWH) on suppressive Combined Antiretroviral Therapy (cART). The aim is to assess safety, tolerability and Impact of low dose Dasatinib, during 24 weeks, on Viral Persistence and Inflammation in this population. Participants will be randomized (2:1) to receive oral Dasatinib 70 mg once daily or matched placebo for 24 weeks. At week 24, Dasatinib will be discontinued and participants will be followed until week 48, in a total of eleven visits. For all participants cART will remain unchanged during the entire study. The hypotheses of the study is that: * Daily administration of a low dose of dasatinib (70 mg once daily) to PWH for 24 weeks will be safe and well tolerated. * Dasatinib will interfere with HIV-1 persistence mechanisms contributing to chronic immune activation and inflammation status in both concordant and immune-discordant virologically suppressed PWH. * Dasatinib antiproliferative effect could have a significant impact on the HIV-1 reservoir size. The primary objective of the study is to evaluate the safety and tolerability of Dasatinib in this setting. Furthermore to evaluate the on-target/biological effect on the reduction of SAM Sterile Alpha-Motif (SAM) and histidine-aspartate (HD) Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1 (SAMHD1) phosphorylation upon in-vitro T-cell activation, and its durability after completion of Dasatinib treatment. Secondary objectives are to evaluate the effect of the described intervention in the on-target/biological effects attributed to dasatinib, as well as on the Inflammation and immune activation, the HIV-1 reservoir, and CD4 and CD8 cell counts. Also to characterize dasatinib concentrations in plasma and its relationships with the observed effects, and to identify predictors of maintenance of dasatinib effects in HIV reservoir and inflammatory biomarkers after dasatinib interruption.

Conditions

• HIV Infection Primary

Interventions

Type	Name	Description
DRUG	Dasatinib 70 mg	Commercially available tablets containing 50 and 20 mg of dasatinib will be used. The tablets will be re-capsulated to keep the study blind
OTHER	Placebo	Maltodextrin capsules with identical size and appearance (shape, size, colour and flavour) as the dasatinib-containing capsules.

Timeline

• Start date: 2023-10-16
• Primary completion: 2025-04-01
• Completion: 2025-04-01
• First posted: 2023-03-22
• Last updated: 2025-09-22

Locations

1 site across 1 country: Spain