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

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 Overview

• Status: Recruiting
• Conditions: Recent HIV-1 Infection
• Intervention / Treatment: Drug: Dasatinib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eva Bonfill; Phone Number: 4198 +34 932275400; Email: bonfill@recerca.clinic.cat

Study Locations

• Spain
  • Barcelona, Spain
    • Recruiting
    • Eva Bonfill
    • Contact: Eva Bonfill; Phone Number: 4198 932 257 400; Email: bonfill@recerca.clinic.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

• HBV positive serology (any marker except HBsAb after vaccination) or HCV positive RNA.
• 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.)
• Resistance to integrase inhibitors (raltegravir, dolutegravir, bictegravir) or analogues

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Dasatinib; Dasatinib monotherapy 70 mg/day, during 16 weeks.
Placebo Comparator: 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.	Drug: Placebo; Placebo during 16 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerance of dasatinib with and without antiretroviral therapy, measured by number of AEs and SAEs	Measured by number of AEs and SAEs	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antiretroviral capacity of dasatinib	Measured by quantification of plasma HIV-1 viral load during 4-week administration of dasatinib monotherapy.	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)	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+.	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.	at week 0, 4, 16 and 52
Pharmacokinetic interactions of coadministration non-boosted integrase inhibitor-based antiretroviral therapy with dasatinib.	Measured by Cmax	at week 1, 2, 3, 4, 8, 12, 16
Pharmacokinetic interactions of coadministration non-boosted integrase inhibitor-based antiretroviral therapy with dasatinib.	Measured by Cmin	at week 1, 2, 3, 4, 8, 12, 16
Impact of dasatinib on markers of senescence	Measured by expression in PBLs of beta-galactosidase, Bcl-2, Histone H2A, p16 and CD87.	at week 0, 4, 16 and 52

Collaborators and Investigators

• Sponsor: Eva Bonfill

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: August 3, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Urogenital Diseases; Genital Diseases; HIV Infections; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: 2021-001288-26

Drug and device information, study documents

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