Evaluating Dasatinib's effects on HIV persistence and inflammation in treated patients

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

This study is testing if a low dose of Dasatinib can help reduce HIV persistence and inflammation in people who are already on treatment for HIV.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fundació Institut Germans Trias i Pujol (other)
• Drugs / interventions: dasatinib, cART, immunotherapy
• Locations: 1 site (Badalona, Barcelona)
• Trial ID: NCT05780073 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety and tolerability of low-dose Dasatinib in individuals with HIV who are on suppressive combined antiretroviral therapy (cART). Participants will be randomly assigned to receive either Dasatinib or a placebo for 24 weeks, with ongoing monitoring for an additional 24 weeks. The study will evaluate the drug's impact on viral persistence, inflammation, and immune activation, as well as its effects on T-cell activation and CD4/CD8 cell counts. The trial will also measure Dasatinib concentrations in plasma to understand its relationship with observed effects.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed HIV-1 infection who have been on stable suppressive cART for at least three years.

Not a fit: Patients who are not on suppressive cART or have not maintained a low viral load may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved management of HIV by reducing viral persistence and inflammation in treated patients.

How similar studies have performed: While the approach of using Dasatinib in this context is novel, other studies have explored similar mechanisms in HIV treatment with varying degrees of success.

Eligibility criteria

Inclusion Criteria:

* 1. Males and females aged at least 18 years on the day of screening.
* 2. Confirmed HIV-1 infection.
* 3. Receiving suppressive cART for at least 3 years (defined as maintained plasma viral load \<50 copies/mL, allowing for isolated blips \[\<200 cop/ml, non-consecutive, representing \<20% total determinations\]).
* 4. Being on the same ART regimen within at least 4 weeks prior to baseline visit.
* 5. Willing and able to be adherent to their ART regimen for the duration of the study.
* 6. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
* 7. In the opinion of the Principal Investigator, the candidate has understood the information provided and can give written Informed Consent.
* 8. 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.
* 9. 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.
* 10. If female, willing to undergo urine pregnancy tests at the designated time points.
* 11. Willing to accept blood draws at time points specified in the Schedule of Events

Exclusion Criteria:

* 1. If female, pregnant or planning a pregnancy during the entire study or lactating.
* 2. Current treatment with ART regimen that includes ritonavir, cobicistat or with any other drug with known relevant drug-drug interactions with dasatinib.
* 3. 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.
* 4. Prior history of exposure to dasatinib or any other Tyrosine Kinase Inhibitor (TKI).
* 5. Prior history of pleural effusion.
* 6. Prior history or clinical manifestations of any physical or psychiatric disorder that could impair the subject's ability to complete the study.
* 7. Any active AIDS-defining disease or progression of HIV-related disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy.
* 8. 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.
* 9. Systemic treatment for cancer within 1 year of study entry.
* 10. Known hypersensitivity to any component of the IMP formulation, or severe or multiple allergies to drugs or pharmaceutical agents.
* 11. Potential participant received or plans to receive:

  1. Licensed live attenuated vaccines within 28 days before or after inflammation and immune biomarkers visit (weeks 0, 2, 24 and 48).
  2. 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).
* 12. Receipt of blood products within 3 months of study entry.
* 13. 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).
* 14. Any other current or prior therapy which, in the opinion of the investigator, would make the individual unsuitable for the study or influence the results of the study.
* 15. Any laboratory abnormalities including:

Hematology:

* Hemoglobin \<10.0 g/dl,
* Absolute neutrophil count ≤3,000 /mm3,
* Platelets ≤100,000/mm3,

Biochemistry:

* Estimated glomerular filtration rate (eGFR) \<60 ml/min,
* Aspartate Transferase (AST) \> 2.5 x upper limit of normal (ULN),
* Alanine Transaminase (ALT) \> 2.5 x ULN,

Microbiology:

* Positive for hepatitis B surface antigen,
* Positive for hepatitis C antibody, unless confirmed clearance of hepatitis C virus (HCV) infection (spontaneous or following treatment)
* Positive serology indicating active syphilis requiring treatment

  * 16. Has a corrected QT interval (QTc interval) ≥470 msec (males) or ≥480 msec (females) upon confirmation on recheck at screening, has a history of risk factors for Torsades de Pointes (eg, heart failure/cardiomyopathy or family history of long QT syndrome), or is taking concomitant medications that prolong the QT/QTc interval.

Where this trial is running

Badalona, Barcelona

• Hospital Universitari Germans Trias i Pujol — Badalona, Barcelona, Spain (RECRUITING)

Study contacts

• Principal investigator: José Moltó, MD, PhD — Fundació Lluita contra les Infeccions - Hospital Universitari Germans Trias i Pujol
• Study coordinator: Beatriz Mothe, MD, PhD

Conditions: HIV Infection Primary, SAMHD1 phosphorylation, T-cell activation, Dasatinib, Suppressive combined Anti Retroviral Treatment