DASATINIB for HIV infection

Inclusion criteria

• {"criterion_text":"- 1.\tMales and females aged at least 18 years on the day of screening.\n- 10.\tIf female, willing to undergo urine pregnancy tests at the designated time points.\n- 11.\tWilling to accept blood draws at time points specified in the Schedule of Events.\n- 2.\tConfirmed HIV-1 infection.\n- 3.\tReceiving 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]).\n- 4.\tBeing on the same ART regimen within at least 4 weeks prior to baseline visit.\n- 5.\tWilling and able to be adherent to their ART regimen for the duration of the study.\n- 6.\tWilling to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.\n- 7.\tIn the opinion of the Principal Investigator, the candidate has understood the information provided and can give written Informed Consent.\n- 8.\tIf heterosexually active female of childbearing potential1, 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 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.\n- 9.\tIf 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 sterility2) 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."}

Exclusion criteria

• {"criterion_text":"- 1.\tIf female, pregnant or planning a pregnancy during the entire study or lactating.\n- 10.\tSystemic treatment for cancer within 1 year of study entry.\n- 11.\tKnown hypersensitivity to any component of the IMP formulation, or severe or multiple allergies to drugs or pharmaceutical agents.\n- 12.\tPotential participant received or plans to receive: a.\tLicensed live attenuated vaccines within 28 days before or after inflammation and immune biomarkers visit (weeks 0, 2, 24 and 48). b.\tother vaccines (eg, tetanus, hepatitis A, hepatitis B, rabies, pneumococcal, recombinant Herpes Zoster, Influenza, COVID-19 vaccines) within 14 days before or after inflammation and immune biomarkers visits (weeks 0, 2, 24 and 48)1.\n- 13.\tReceipt of blood products within 3 months of study entry.\n- 14.\tCurrent 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).\n- 15.\tAny 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.\n- 16.\tAny laboratory abnormalities including: Hematology ·\tHemoglobin <10.0 g/dl, ·\tabsolute neutrophil count ≤3,000 /mm3, ·\tPlatelets ≤100,000/mm3, Biochemistry ·\teGFR <60 ml/min, ·\tAST > 2.5 x ULN, ·\tALT > 2.5 x ULN, Microbiology ·\tPositive for hepatitis B surface antigen, ·\tPositive for hepatitis C antibody, unless confirmed clearance of HCV infection (spontaneous or following treatment) ·\tPositive serology indicating active syphilis requiring treatment2\n- 17.\tHas a 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.\n- 2.\tCurrent treatment with ART regimen that includes ritonavir, cobicistat or with any other drug with known relevant drug-drug interactions with dasatinib.\n- 3.\tHas received any immunotherapy with intent to cure or prevent HIV, including monoclonal antibodies, therapeutic or preventive vaccines within 6 months prior to baseline visit.\n- 4.\tPrior history of exposure to dasatinib or any other TKI.\n- 5.\tPrior history of pleural effusion.\n- 6.\tPrior history or clinical manifestations of any physical or psychiatric disorder that could impair the subject’s ability to complete the study.\n- 7.\tAny active AIDS-defining disease or progression of HIV-related disease, except cutaneous Kaposi’s sarcoma not requiring systemic therapy.\n- 8.\tOngoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal, or penile intraepitelial neoplasia.\n- 9.\tOngoing diabetes mellitus with poor metabolic control (requiring insulin therapy initiation, hospitalization or documented HbA1c >8% within the last 3 months)."}

Primary endpoints

• {"endpoint_text":"- ·\tProportion of participants that develop Grade 3 or 4 treatment-related adverse events or laboratory abnormalities during the study, based on the CTCAE v5.0 grading scale.","definition_or_measurement_approach":"Adverse events and laboratory abnormalities graded using CTCAE v5.0 (Noviembre 2017); proportion of participants developing Grade 3 or 4 treatment-related events during study period."}
• {"endpoint_text":"- ·\tProportion of SAMHD1 phosphorylation in CD4+ T cells upon in-vitro T cell activation at weeks 0, 2, 12, 24, 28, 36 and 48.","definition_or_measurement_approach":"Measurement of SAMHD1 phosphorylation in CD4+ T cells after in-vitro T-cell activation at specified timepoints (weeks 0, 2, 12, 24, 28, 36, 48); endpoint expressed as proportion of phosphorylation."}

Secondary endpoints

• {"endpoint_text":"- Antiviral effect of dasatinib and its durability:Proviral reactivation capacity upon in-vitro T-cell activation, Resistance to HIV infection, Homeostatic proliferation, Immunomodulatory effects","definition_or_measurement_approach":"Measures include proviral reactivation capacity upon in-vitro T-cell activation, assays for resistance to HIV infection, assessments of homeostatic proliferation and immunomodulatory effects (methods as per protocol)."}
• {"endpoint_text":"- Impact of dasatinib and its durability on: Inflammation and immune activation, HIV-1 reservoir, CD4+ T cell populations","definition_or_measurement_approach":"Assessments of inflammatory and immune activation biomarkers, quantification of HIV-1 reservoir, and CD4+ T cell counts/populations at scheduled visits."}
• {"endpoint_text":"- Pharmacokinetics of dasatinib: ·\tDasatinib concentrations in plasma at weeks 0, 2, 12 and 24.","definition_or_measurement_approach":"Plasma concentrations of dasatinib measured at weeks 0, 2, 12 and 24 to characterize pharmacokinetics and relate concentrations to biological effects."}

Spain

Earliest CTIS Part Ii Submission Date

19-06-2024

Latest Decision Or Authorization Date

28-06-2024

Processing Time Days

9

Number Of Sites

1

Number Of Participants

60

Primary sponsor

Full Name

Instituto De Investigacion En Ciencias De La Salud Germans Trias I Pujol

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain

Contract research organisations

Responsibilities

Study CRO (unnamed) will have access to the randomization list and related blinding/randomization responsibilities as described in the protocol.

Third parties

• {"country":"Spain","full_name":"Instituto de Salud Carlos III-Ministero Ciencia e Innovación-Ayudas Investigación Clínica Indep.","duties_or_roles":"Source of monetary support / funding","organisation_type":""}