Clinical Trial To Evaluate The Safety And Efficacy Of Dasatinib To Reduce HIV-1 Reservoir, Chronic Inflammation, And Immune Senescence In People With HIV On Long-Term Antiretroviral Treatment.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instituto De Salud Carlos III

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2026-06-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate changes in CD4, CD8 and CD56+ cell counts and activation/exhaustion markers during treatment with dasatinib.

Secondary objectives 11

1. To explore changes in CD4⁺, CD8⁺, and CD56⁺ cell counts and their activation/exhaustion profiles at additional time points throughout the study.
2. To determine the safety and tolerability of 50 mg/day dasatinib in combination with ART in people with HIV during 24 weeks.
3. To evaluate changes in T cell activation markers CD25 and CD69 throughout dasatinib treatment and follow-up.
4. To assess the effect of dasatinib on SAMHD1 phosphorylation levels over the course of treatment and during follow-up.
5. To characterize the viral reservoir during and after treatment with dasatinib.
6. To calculate the effect of dasatinib on the rate of decay on the proviral reservoir by mathematical model.
7. To determine the changes in the levels of proinflammatory and homeostatic cytokines during and after treatment with dasatinib.
8. To analyze the effect of dasatinib on immune exhaustion and senescence during and after treatment.
9. To evaluate the CD4+ T cell distribution and trafficking biomarkers as measure of the capacity of dasatinib to flush lymphocytes from the secondary lymphoid organs and tissues to the peripheral blood.
10. To evaluate the effect of dasatinib on susceptibility to infection of monocyte-derived macrophages during and after treatment.
11. To evaluate the effect of dasatinib on NK cell trained immunity.

Conditions and MedDRA coding

HIV-1 infection

Study design 1 period

Regulatory references

Plan to share IPD

No

IPD plan description

Not applicable

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. The participant is ≥ 18 years old and informed and able to understand the full nature and purpose of the study, including possible risks and side effects, and is given ample time and opportunity to read and understand this information. Subject has the ability and agrees to cooperate with the Investigator and must sign and date the written informed consent prior to performing any of the screening procedures.
2. Confirmed HIV-1 infection.
3. On suppressive ART for between 1 and 10 years, defined as sustained plasma HIV-1 RNA levels below the limit of detection for at least the last 6 months. Isolated, non-consecutive viral blips <200 copies/mL are allowed if they represent less than 20% of all viral load determinations during this period.
4. Participants must present at screening a CD4 count >500 cells/mm3 and/or CD4/CD8=1.0±0.2.
5. Stable ART regimen for at least six months prior to the screening visit and during the screening period.
6. Participants must commit to consistent adherence to ART and to comply with the study treatment regimen throughout the 24-week treatment period.
7. Subject and their partner of childbearing potential must agree to use a highly effective method of contraception throughout the study as specified in Section 7. A man is of childbearing potential if, in the opinion of the Investigator, he is sexually active. Menopausal females must have experienced their last period more than 1 year prior to the date of informed consent to be classified as not of childbearing potential (a postmenopausal state is defined as cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause).

Exclusion criteria 13

1. Participants are not willing or able to comply with either: all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, or other study procedures.
2. Intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, pleural or pericardial effusion, pulmonary edema, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, QT Prolongation (QTcF >450 msec for males or >470 msec for females) or use of QT-prolonging medications, or psychiatric illness/social situations that would limit compliance with study requirements.
3. History of clinically significant ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes.
4. History of clinically significant pleural effusion.
5. History of clinically significant bleeding disorder including congenital bleeding disorders, acquired bleeding disorder within the first year of life and ongoing or recent (≤ 3 months) clinically significant gastrointestinal bleeding.
6. Laboratory abnormalities at screening: a. Hemoglobin < 11 g/dl b. Platelet count < 75,000/µL c. Absolute neutrophil count (ANC) <1,000 cells/µL d. ALT and/or AST > 1.5 x ULN e. Hypokalemia according to local laboratory normality values. f. Hypomagnesemia according to local laboratory normality values.
7. Known infection with hepatitis B or hepatitis C: positive for hepatitis B surface antigen, positive for hepatitis C antibody (without treatment with Direct Action Antivirals (DAA) or spontaneous clearance).
8. Lactose Intolerance or Malabsorption Syndrome: Patients with hereditary galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
9. Patients in current treatment with drugs that interfere with dasatinib metabolized mainly by CYP3A4 and those that induce CYP3A4. A list of prohibited medications can be found in section 7.5.
10. Pregnant or breastfeeding women, where pregnancy is defined as the state of a female after conception and until the termination of gestation
11. Any other condition that, in the opinion if the Investigator, may interfere with the efficacy and/or safety evaluation of the trial.
12. Any condition or situation precluding or interfering with the compliance with the protocol.
13. Participant is currently enrolled or has enrolled in a clinical trial three months prior to inclusion in the current study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Changes in CD4, CD8, and CD56+ cell counts and activation/exhaustion markers from baseline values to 2-3 days and 24 weeks of dasatinib treatment and placebo.

Secondary endpoints 11

1. Changes in CD4⁺, CD8⁺, and CD56⁺ cell counts and activation/exhaustion markers from baseline values to weeks 4, 12, 28, 36, and 48, in both the dasatinib and placebo groups.
2. Incidence, nature and severity of adverse events during study period (clinical and laboratory).
3. Changes in the expression levels of CD25 and CD69 activation markers from baseline to days 2–3, and weeks 4, 12, 24, 28, 36, and 48, in both the dasatinib and placebo groups.
4. Changes in phosphorylated SAMHD1 (Thr592) expression levels at weeks 4, 12, 24, 28, 36, and 48, in both the dasatinib and placebo groups.
5. Characterization of the viral reservoir at weeks 4, 12, 24, 28, 36 and 48 of the study, including reservoir size and composition, reactivation capacity, integration sites, and HIV evolution and diversity.
6. Rate of decay of the proviral reservoir during and after dasatinib treatment, as determined by a mathematical model analyzing longitudinal changes in proviral DNA levels at weeks 4, 12, 24, 28, 36 and 48.
7. Changes in the levels of inflammation markers such as IL-6, CRP, TNFα and sCD163 during and after dasatinib treatment, assessed at weeks 4, 12, 24, 28, 36 and 48.
8. Changes in immune exhaustion and senescence markers during and after dasatinib treatment, assessed at weeks 4, 12, 24, 28, 36 and 48.
9. Changes in CD4+ T cell distribution and trafficking biomarkers, including CCR7, CD45RA, CD49a, CD103, CD101, CXCR6, CX3CR1, and PD-1 expression on CD69+ (tissue-resident memory T cells) and CD69- (TEM/TEMRA memory T cells), assessed at day 2-3 and weeks 4, 12, 24, 28, 36 and 48.
10. Changes in the susceptibility of monocyte-derived macrophages to HIV-1 infection during and after dasatinib treatment, assessed at weeks 4, 12, 24, and 48 by luminescence and flow cytometry analysis of intracellular HIV-1 core protein and phosphorylated SAMHD1 (Thr592).
11. Changes in NK cell cytotoxic activity and activation/exhaustion markers assessed at weeks 4, 12, 24, 28, 36 and 48 by microscopy and flow cytometry.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instituto De Salud Carlos III

Sponsor organisation

Instituto De Salud Carlos III

Address

Pab 6 Sotano, Avenida Monforte De Lemos 5 Avenida Monforte De Lemos 5

City

Madrid

Postcode

28029

Country

Spain

Scientific contact point

Organisation

Instituto De Salud Carlos III

Contact name

María Teresa Coiras López

Public contact point

Organisation

Instituto De Salud Carlos III

Contact name

María Teresa Coiras López

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications