DASATINIB for Asymptomatic HIV-1 infection

Inclusion criteria

• {"criterion_text":"-Age range: 18 to 65 years."}
• {"criterion_text":"-Documented asymptomatic HIV-1 infection of more than 3 months duration (all patients must have a positive Western blot, including the p31 band, indicating an infection of more than 90 days duration)."}
• {"criterion_text":"-Not having received ART."}
• {"criterion_text":"-CD4 T lymphocyte count > 350 / μl."}
• {"criterion_text":"-Patient giving written informed consent."}

Exclusion criteria

• {"criterion_text":"-Active HBV (HBsAg+ or DNA+) and/or HCV (RNA+) infection on screening."}
• {"criterion_text":"-ALT> 2 UNL, glomerular filtration rate <70 mL / 1.73 m2, leukocytes <4000 / mm3, total lymphocyte count <1000 / mm3, platelets <100,000 / mm3 or Hg <12g / dL."}
• {"criterion_text":"-Pregnancy or active breastfeeding"}
• {"criterion_text":"-Ongoing or previous pleural effusion"}
• {"criterion_text":"-Chronic obstructive pulmonary disease, bronchial asthma or recent chest trauma."}
• {"criterion_text":"-History of gastrointestinal or other bleeding."}
• {"criterion_text":"-Any concomitant treatment with potentially dangerous drug interaction with dasatinib."}
• {"criterion_text":"-Any clinical condition, at the opinion of the investigator, contraindicating participation (for example, active neoplastic disease, active concomitant infection, etc.)"}

Primary endpoints

• {"endpoint_text":"-The primary endpoint of the study is to assess the safety and tolerability of dasatinib with and without antiretroviral therapy using the incidence of AA.","definition_or_measurement_approach":"Assessment of safety and tolerability of dasatinib with and without antiretroviral therapy using the incidence of AA (as stated: \"using the incidence of AA\")."}

Secondary endpoints

• {"endpoint_text":"-Immunological endpoints: -immune recovery (CD4 subpopulation levels). -inflammatory markers (ultra-sensitive CRP, IL6, TNF alpha) -immune activation (CD4/CD8, CD25, CD69, CD38, HLA-DR+) -bacterial translocation (rsCD163) -levels of NK-mediated cytotoxic activity (NK phenotyping and in vitro replication inhibition tests).","definition_or_measurement_approach":"Measurement of immune recovery via CD4 subpopulation levels; inflammatory markers (ultra-sensitive CRP, IL6, TNF alpha); markers of immune activation (CD4/CD8, CD25, CD69, CD38, HLA-DR+); bacterial translocation (rsCD163); NK activity via NK phenotyping and in vitro replication inhibition tests."}
• {"endpoint_text":"-Virological endpoints: -decline in HIV viral load prior to ART initiation (4 weeks of dasatinib monotherapy) -impact on the viral reservoir (integrated DNA, genetically intact virus, residual and induced viral replication and determination of integration sites) -SAMHD1 phosphorylation levels","definition_or_measurement_approach":"Measurement of plasma HIV-1 viral load decline during 4 weeks of dasatinib monotherapy; assessment of viral reservoir measures (integrated DNA, genetically intact virus, residual/induced viral replication, integration site determination); measurement of SAMHD1 phosphorylation levels."}
• {"endpoint_text":"-Senescence endpoints: -Expression in PBLs of beta-galactosidase, Bcl-2, Histone H2A, p16 and CD87.","definition_or_measurement_approach":"Measurement of senescence marker expression in peripheral blood leukocytes (PBLs): beta-galactosidase, Bcl-2, Histone H2A, p16, CD87."}

Spain

Earliest CTIS Part Ii Submission Date

25-11-2024

Latest Decision Or Authorization Date

11-12-2024

Processing Time Days

16

Number Of Sites

6

Number Of Participants

24

Primary sponsor

Full Name

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain