Safety, Tolerance and Antiretroviral Activity of Dasatinib: a Pilot Clinical Trial in Patients With Recent HIV-1 Infection
- Registration Number
- NCT05527418
- Lead Sponsor
- Eva Bonfill
- Brief Summary
Study to evaluate the safety, tolerability and antiretroviral activity of a new therapeutic strategy, based on the administration of dasatinib, an ITK, in patients with recent (3-12 months) asymptomatic HIV-1 infection.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 24
- 18 to 65 years.
- Documented asymptomatic HIV-1 infection of 3-12 months duration (all patients must have a positive Western blot, including the p31 band whose appearance indicates infection of more than 90 days duration).
- Not having received ART
- CD4 T-lymphocyte count> 350 / μl
- Patient giving written informed consent
- Active HBV (HBsAg+ or DNA+) and/or HCV (RNA+) infection in screening.
- 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.
- Pregnancy or active breastfeeding
- Ongoing or previous pleural effusion
- Chronic obstructive pulmonary disease, bronchial asthma or recent chest trauma.
- History of gastrointestinal or other bleeding.
- Any concomitant treatment with potentially dangerous drug interaction with dasatinib.
- Any clinical condition, at the opinion of the investigator, contraindicating participation (for example,
- Active neoplastic disease, active concomitant infection, etc.)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo monotherapy will be given for 4 weeks. Antiretroviral therapy (ART) based on unboosted integrase inhibitors will be initiated at week 4 (S4) and placebo will be continued with ART until week 12. Dasatinib Dasatinib Dasatinib monotherapy (70 mg/day) will be given for 4 weeks. Antiretroviral therapy (ART) based on unboosted integrase inhibitors will be initiated at week 4 (S4) and dasatinib will be continued with ART until week 12.
- Primary Outcome Measures
Name Time Method Safety and tolerance of dasatinib with and without antiretroviral therapy, measured by number of AEs and SAEs 52 weeks Measured by number of AEs and SAEs
- Secondary Outcome Measures
Name Time Method Antiretroviral capacity of dasatinib at week 0 and 4 Measured by quantification of plasma HIV-1 viral load during 4-week administration of dasatinib monotherapy.
Changes in the viral reservoirs of patients with recent HIV-1 infection induced by dasatinib administration. at week 0, 4, 16 and 52 Measured by changes in the viral reservoirs (integrated DNA, genetically intact virus, residual and induced viral replication and determination of integration sites)
Changes in markers of inflammation and immune activation induced by dasatinib administration. at week 0, 4, 16 and 52 Measured by changes in ultra-sensitive CRP, IL6, TNF alpha and CD4/CD8, CD25, CD69, CD38, HLA-DR+.
Changes in SAMHD1 phosphorylation levels and cytotoxic activity against HIV-1 induced by dasatinib. at week 0, 4, 16 and 52 Measured by NK phenotyping and in vitro replication inhibition tests.
Pharmacokinetic interactions of coadministration non-boosted integrase inhibitor-based antiretroviral therapy with dasatinib. at week 1, 2, 3, 4, 8, 12, 16 Measured by Cmin
Impact of dasatinib on markers of senescence at week 0, 4, 16 and 52 Measured by expression in PBLs of beta-galactosidase, Bcl-2, Histone H2A, p16 and CD87.
Trial Locations
- Locations (1)
Eva Bonfill
🇪🇸Barcelona, Spain