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

NCT05780073 | Completed Phase 2 DMC

• 1 other identifier: BCN04-Dasa
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV Infection Primary

Keywords

SAMHD1 phosphorylation; T-cell activation; Dasatinib; Suppressive combined Anti Retroviral Treatment

Outcome Measures

Primary Outcomes (3)

• Grade 3 or 4 treatment-related adverse events or laboratory abnormalities during the study (based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grading scale).

  Proportion of participants (People with HIV on suppressive Combined Antiretroviral Therapy) that develop Grade 3 or 4 treatment-related adverse events or laboratory abnormalities during the study, based on the CTCAE v5.0 grading scale.

  From baseline (0) to week 48

• Changes in SAMHD1 (SAM And HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1) phosphorylation in CD4+ T cells upon in-vitro T cell activation.

  Proportion of SAM (Sterile alpha-motif ) and HD (histidine-aspartate) Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1 (SAMHD1) phosphorylation in CD4+ T cells upon in-vitro T cell activation.

  From Baseline (0) to week 24

• Changes in SAMHD1 (SAM And HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1) phosphorylation in CD4+ T cells upon in-vitro T cell activation.

  Proportion of SAM (Sterile alpha-motif ) and HD (histidine-aspartate) Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1 (SAMHD1) phosphorylation in CD4+ T cells upon in-vitro T cell activation.

  From Baseline (0) to week 48

Secondary Outcomes (16)

• Proviral reactivation capacity upon in-vitro T-cell activation: Proportion of intracellular HIV-1 core antigen in CD4+ T cells

  At weeks 0 (baseline) , 2, 24 and 48 weeks

• Proviral reactivation capacity upon in-vitro T-cell activation: Frequency of HIV-1 p24 production

  At weeks 0 (baseline), 2, 24 and 48 weeks

• Resistance to HIV infection: Frequency of CD4+ T cells infection by NL4-3_wild type strain

  At weeks 0 (baseline), 2, 24 and 48 weeks

• Plasma levels of homeostatic cytokines (interleukin-IL) IL-2, IL-7, IL-15, IL-21

  At weeks 0 (baseline), 2, 24 and 48 weeks

• Antiviral effect of Dasatinib and its durability (Immunomodulatory effects) (Presence of cytotoxic activity in natural killer (NK) and CD8+ T cells).

  At weeks 0 (baseline) , 24 and 48 weeks

Other Outcomes (2)

• Changes in the contributors to the reservoir repertoire

  At weeks 0(baseline), 24 and 48 weeks

• Quantification of herpes viruses-specific immunoglobulin G (IgG) (CMV/EBV)

  At weeks 0(baseline), 24 and 48 weeks

Study Arms (2)

Dasatinib

EXPERIMENTAL

Dasatinib 70 mg/daily, orally administered, for 24 weeks

Drug: Dasatinib 70 mg

Placebo

PLACEBO COMPARATOR

Investigational Medicinal Product-like appearance capsule containing an inert substance,orally administered, once daily, for 24 weeks

Other: Placebo

Interventions

Dasatinib 70 mg DRUG

Commercially available tablets containing 50 and 20 mg of dasatinib will be used. The tablets will be re-capsulated to keep the study blind

Also known as: Experimental

Dasatinib

Placebo OTHER

Maltodextrin capsules with identical size and appearance (shape, size, colour and flavour) as the dasatinib-containing capsules.

Also known as: Control

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Males and females aged at least 18 years on the day of screening.
• \. Confirmed HIV-1 infection.
• \. Receiving suppressive cART for at least 3 years (defined as maintained plasma viral load \<50 copies/mL, allowing for isolated blips \[\<200 cop/ml, non-consecutive, representing \<20% total determinations\]).
• \. Being on the same ART regimen within at least 4 weeks prior to baseline visit.
• \. Willing and able to be adherent to their ART regimen for the duration of the study.
• \. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
• \. In the opinion of the Principal Investigator, the candidate has understood the information provided and can give written Informed Consent.
• \. If heterosexually active female of childbearing potential, using an effective method of contraception (hormonal contraception, intra-uterine device (IUD), or anatomical sterility in self or partner) from 14 days prior to the first Investigational Medicinal Product (IMP) administration and commit to use it until 3 months after the last IMP administration. All female candidates of childbearing potential who are not heterosexually active at screening, must agree to utilize an effective method of contraception if they become heterosexually active during the study.
• \. If heterosexually active male, regardless of reproductive potential, sterilized or agree on the use of an effective method of contraception by his female partner (hormonal contraception, intra-uterine device (IUD), or anatomical sterility) from the day of the first IMP administration until 3 months after the last IMP administration. All male candidates who are not heterosexually active at screening, must agree to utilize an effective method of contraception if they become heterosexually active during the study.
• \. If female, willing to undergo urine pregnancy tests at the designated time points.
• \. Willing to accept blood draws at time points specified in the Schedule of Events

You may not qualify if:

• \. If female, pregnant or planning a pregnancy during the entire study or lactating.
• \. Current treatment with ART regimen that includes ritonavir, cobicistat or with any other drug with known relevant drug-drug interactions with dasatinib.
• \. Has received any immunotherapy with intent to cure or prevent HIV, including monoclonal antibodies, therapeutic or preventive vaccines within 6 months prior to baseline visit.
• \. Prior history of exposure to dasatinib or any other Tyrosine Kinase Inhibitor (TKI).
• \. Prior history of pleural effusion.
• \. Prior history or clinical manifestations of any physical or psychiatric disorder that could impair the subject's ability to complete the study.
• \. Any active AIDS-defining disease or progression of HIV-related disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy.
• \. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal, or penile intraepithelial neoplasia.
• \. Systemic treatment for cancer within 1 year of study entry.
• \. Known hypersensitivity to any component of the IMP formulation, or severe or multiple allergies to drugs or pharmaceutical agents.
• \. Potential participant received or plans to receive:
• Licensed live attenuated vaccines within 28 days before or after inflammation and immune biomarkers visit (weeks 0, 2, 24 and 48).
• other vaccines (eg, tetanus, hepatitis A, hepatitis B, rabies, pneumococcal, recombinant Herpes Zoster, Influenza, Coronavirus Disease -19 \[COVID-19\] vaccines) within 14 days before or after inflammation and immune biomarkers visits (weeks 0, 2, 24 and 48).
• \. Receipt of blood products within 3 months of study entry.
• \. Current or recent use (within last 3 months) of interferon or systemic corticosteroids or other immunosuppressive agents (use on inhaled steroids for asthma or topic steroids for localized skin conditions are permitted).

Sponsors & Collaborators

• Fundació Institut Germans Trias i Pujol: lead
• Spanish Clinical Research Network - SCReN: collaborator
• IrsiCaixa: collaborator
• University of Turin, Italy: collaborator
• Instituto de Salud Carlos III: collaborator
• Germans Trias i Pujol Hospital: collaborator
• Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia: collaborator

Study Sites (1)

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

MeSH Terms

Interventions

Dasatinib

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• José Moltó, MD, PhD

  Fundació Lluita contra les Infeccions - Hospital Universitari Germans Trias i Pujol

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Dasatinib capsules re-capsulated with identical appearance with Placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: March 22, 2023
• Study Start: October 16, 2023
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)