Baricitinib for HIV-1 infection

Inclusion criteria

• {"criterion_text":"- Males and females aged between 18 and 65 years on the day of the screening visit."}
• {"criterion_text":"- If positive IgG for varicella zoster, adequate herpes zoster vaccination at least 4 weeks prior to week 0 visit."}
• {"criterion_text":"- Willing to accept blood draws at time points specified in the Schedule of Events."}
• {"criterion_text":"- Confirmed HIV-1 infection."}
• {"criterion_text":"- Receiving suppressive cART for at least 2 years (defined as maintained plasma viral load <50 copies/mL, allowing for isolated blips [<200 cop/ml, non-consecutive, representing <20% total determinations])."}
• {"criterion_text":"- Being on the same cART regimen within at least 4 weeks prior to baseline visit (week 0)."}
• {"criterion_text":"- Willing and able to be adherent to their cART regimen for the duration of the study."}
• {"criterion_text":"- Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study."}
• {"criterion_text":"- In the opinion of the clinical investigator, the candidate has understood the information provided and can give written Informed Consent."}
• {"criterion_text":"- If heterosexually active female of childbearing potential1, using an effective method of contraception different from hormonal contraception (intra-uterine device (IUD), anatomical sterility in self or partner or sexual abstinence) 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 sexually active with men at screening, must agree to utilize an effective method of contraception if they become sexually active during the study."}
• {"criterion_text":"- If female of childbearing potential, willing to undergo urine pregnancy tests at the designated time points."}

Exclusion criteria

• {"criterion_text":"- If female of childbearing potential, pregnant or planning a pregnancy during the entire study or lactating."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Prior history of thrombotic events (deep venous thrombosis, pulmonary embolism, or arterial thrombosis) or known inherited prothrombotic disorders (Factor V Leiden, prothrombin G2021A mutation, antithrombin deficiency, protein S deficiency, protein C deficiency, etc.)"}
• {"criterion_text":"- Current use of combined hormonal contraceptives or substitutive hormonal treatment."}
• {"criterion_text":"- History of any of the following cardiovascular diseases: myocardial infarction, unstable angina, congestive heart failure, uncontrolled arrhythmias, cardiac revascularization, stroke, uncontrolled hypertension, or uncontrolled diabetes within 6 months."}
• {"criterion_text":"- Current smokers over 10 cigarettes per day or former smokers with a history of smoking more than 10 pack-years, unless they quit smoking more than 15 years ago."}
• {"criterion_text":"- 15.\tPositive hepatitis C IgG, unless confirmed clearance of HCV infection (undetectable plasma viral load, spontaneous or following treatment)."}
• {"criterion_text":"- Chronic hepatitis B, defined as positive hepatitis B surface antigen (HBsAg); or past hepatitis B, defined as positive hepatitis B core antibody (HBcAb), unless ART regimen contains FTC/TFV during the study."}
• {"criterion_text":"- Symptomatic herpes zoster or recurrent genital herpes within 24 weeks from screening, or any history of disseminated herpes simplex, disseminated herpes zoster, ophthalmic zoster, or CNS zoster."}
• {"criterion_text":"- History of active, past, or latent tuberculosis, confirmed through medical history, clinical records, or positive TB IGRAs by QuantiFERON test, unless documented preventive TB treatment with 6 or 9 months of daily isoniazid, or a 3-month regimen of weekly rifapentine plus isoniazid, or a 3-month regimen of daily isoniazid plus rifampicin."}
• {"criterion_text":"- Any laboratory abnormalities including: Hematology: - Hemoglobin <10.0 g/dl, - Absolute neutrophil count ≤1,000 /mm3, -Absolute lymphocyte count ≤500 /mm3, - Platelets >450,000/mm3, Biochemistry: -\teGFR <30 ml/min, -\tAST > 2.5 x ULN, -\tALT > 2.5 x ULN"}
• {"criterion_text":"- Prior history or clinical manifestations of any physical or psychiatric disorder that could impair the subject’s ability to complete the study."}
• {"criterion_text":"- Any active AIDS-defining disease or progression of HIV-related disease, except cutaneous Kaposi’s sarcoma not requiring systemic therapy."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Systemic treatment for cancer within 1 year of study entry."}
• {"criterion_text":"- Known hypersensitivity to any component of the IMP formulation, or severe or multiple allergies to drugs or pharmaceutical agents."}
• {"criterion_text":"- Potential participant received or plans to receive: i. Licensed live attenuated vaccines within 28 days before or after inflammation and immune biomarkers visit (weeks 0 and 12). ii. Other 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 and 12)."}
• {"criterion_text":"- Receipt of blood products within 3 months of study entry."}
• {"criterion_text":"- 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)."}

Primary endpoints

• {"endpoint_text":"- Proportion of participants developing Grade 3 or 4 treatment-related adverse events or laboratory abnormalities during the study, based on the Division of AIDS (DAIDS) Table for grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 [July 2017]. Safety laboratory tests will be performed at weeks 0, 4, 12 and 24.","definition_or_measurement_approach":"Grading based on DAIDS Table for grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (July 2017). Safety laboratory tests scheduled at weeks 0, 4, 12 and 24."}
• {"endpoint_text":"- Levels of pSTAT 1, 3 and 5 in CD4+ T cells, at weeks 0 and 12 measured by Flow cytometry.","definition_or_measurement_approach":"Measured by flow cytometry in CD4+ T cells at weeks 0 and 12."}

Secondary endpoints

• {"endpoint_text":"- Changes in levels of BCL-2 in CD4+ T cells, at weeks 0 and 12 measured by Flow cytometry.","definition_or_measurement_approach":"Measured by flow cytometry in CD4+ T cells at weeks 0 and 12."}
• {"endpoint_text":"- Changes in levels of IFITM2, pJAK1/2, cleaved-caspase 3 and other pro- apoptotic markers in CD4+ T cells, at weeks 0 and 12 measured by Western blot.","definition_or_measurement_approach":"Measured by Western blot in CD4+ T cells at weeks 0 and 12."}
• {"endpoint_text":"- Changes in total and intact proviral HIV-1 DNA (IPDA) in CD4 T cells at weeks 0 and 12.","definition_or_measurement_approach":"Quantification of total and intact proviral HIV-1 DNA (IPDA) in CD4+ T cells at weeks 0 and 12."}
• {"endpoint_text":"- Changes in soluble plasma levels of proinflammatory biomarkers (such as IL-2, IL-6, IL-7, IL-15, IL-8, TNFa, IFNg and sCD14) and anti-inflammatory biomarkers (such as IL-10, IL-4, IL-13), at weeks 0 and 12.","definition_or_measurement_approach":"Plasma soluble biomarker quantification at weeks 0 and 12 (specific assays not further specified)."}
• {"endpoint_text":"- Changes in T cell immune subsets and frequencies of T cells expressing activation, exhaustion and senescence markers at weeks 0 and 12 measured by multiparametric flow cytometry.","definition_or_measurement_approach":"Measured by multiparametric flow cytometry in T cell subsets at weeks 0 and 12."}
• {"endpoint_text":"- Baricitinib concentrations in plasma at weeks 4 and 12.","definition_or_measurement_approach":"Plasma pharmacokinetic concentration measurements of baricitinib at weeks 4 and 12."}

Spain

Earliest CTIS Part Ii Submission Date

08-04-2025

Latest Decision Or Authorization Date

09-05-2025

Processing Time Days

31

Number Of Sites

1

Number Of Participants

30

Primary sponsor

Full Name

Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain

Third parties

• {"country":"","full_name":"Spanish Ministery of Health (Fondo de Investigaciones Sanitarias 2024)","duties_or_roles":"Source of monetary support / funder","organisation_type":""}