Safety, Tolerance and Antiretroviral Activity of Dasatinib: a Pilot Clinical Trial in Patients With Recent HIV-1 Infection

Phase 2RecruitingNCT05527418

Eva Bonfill24 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Recent HIV-1 Infection

Interventions

DasatinibDRUG

Dasatinib monotherapy 70 mg/day, during 16 weeks.

PlaceboDRUG

Placebo during 16 weeks.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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.)

Locations (1)

Eva Bonfill

Barcelona, Spain

RECRUITING

Outcomes

Primary Outcomes

Safety and tolerance of dasatinib with and without antiretroviral therapy, measured by number of AEs and SAEs

Measured by number of AEs and SAEs

Time frame: 52 weeks

Secondary Outcomes

Antiretroviral capacity of dasatinib

Measured by quantification of plasma HIV-1 viral load during 4-week administration of dasatinib monotherapy.

Time frame: at week 0 and 4

Changes in the viral reservoirs of patients with recent HIV-1 infection induced by dasatinib administration.

Measured by changes in the viral reservoirs (integrated DNA, genetically intact virus, residual and induced viral replication and determination of integration sites)

Time frame: at week 0, 4, 16 and 52

Changes in markers of inflammation and immune activation induced by dasatinib administration.

Measured by changes in ultra-sensitive CRP, IL6, TNF alpha and CD4/CD8, CD25, CD69, CD38, HLA-DR+.

Time frame: at week 0, 4, 16 and 52

Changes in SAMHD1 phosphorylation levels and cytotoxic activity against HIV-1 induced by dasatinib.

Measured by NK phenotyping and in vitro replication inhibition tests.

Time frame: at week 0, 4, 16 and 52

Pharmacokinetic interactions of coadministration non-boosted integrase inhibitor-based antiretroviral therapy with dasatinib.

Measured by Cmax

Time frame: at week 1, 2, 3, 4, 8, 12, 16

Pharmacokinetic interactions of coadministration non-boosted integrase inhibitor-based antiretroviral therapy with dasatinib.

Central Contacts

Eva Bonfill

CONTACT

+34 932275400 bonfill@recerca.clinic.cat

Data from ClinicalTrials.gov

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