Safety and Impact of Baricitinib on Cell Surivival Pathways, HIV-1 Reservoir and Inflamation in People With HIV-1

NCT07028385 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: BCN05-Bari2024-520159-26-00
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this exploratory clinical trial is to evaluate the safety and tolerability of bariticinib administered at 2 mg once daily during 12 weeks in 30 people living with HIV-1 (PWH) on suppressive antiretroviral therapy (ART) and to evaluate changes in levels of phosphorylated STAT (pSTAT) after 12 weeks of treatment with bariticinib. The main questions it aims to answer are:

• The safety and tolerability of bariticinib
• To evaluate the effects of bariticinib on T-cells (HIV-1 reservoirs, apoptosis, inflamation, activation and exhaustion).
• To characterize bariticinib pharmacokinetics in plasma. Participants will be treated with pral Barticinib 2mg or matched Placebo daily for 12 weeks. Suppressive cART will remain unchanged during the entire study. Participants will be followed until week 24, in a total of 8 visits.

Conditions

HIV

Keywords

bariticinib; HIV; ctl resistance; jak/stat inhibitor; bcl2

Outcome Measures

Primary Outcomes (2)

• To evaluate the safety and tolerability of baricitinib.

  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 \[July 2017\].

  From baseline (week 0) to week 12

• To evaluate changes in levels of phosphorylated STAT (pSTAT) in CD4+ T cells, as a pharmacodynamic biomarker of baricitinib activity.

  Levels of pSTAT 1, 3 and 5 in CD4+ T cells measured by Flow cytometry.

  From baseline (week 0) to week 12

Secondary Outcomes (6)

• To evaluate the effect of baricitinib on proapoptotic pathways mediated by BCL-2.

  From baseline (week 0) to week 12

• To evaluate the effect of baricitinib on JAK/STAT signaling pathway

  From baseline (week 0) to week 12

• To evaluate the effect of baricitinib on the HIV-1 reservoir.

  From baseline (week 0) to week 12

• To evaluate the impact of baricitinib on homeostatic cytokines, inflammatory biomarkers and cell death markers.

  From baseline (week 0) to week 12

• To evaluate the effects of baricitinib in immune cell subsets.

  From baseline (week 0) to week 12

Other Outcomes (3)

• To evaluate the effect of baricitinib in HIV-1 specific T cells.

  From baseline (week 0) to week 12

• To evaluate the effect of baricitinib on CD4 sensitivity to CTL killing.

  From baseline (week 0) to week 12

• To assess the impact of baricitinib on transcriptomic signatures related to survival, apoptotic regulation (both pro- and anti-apoptotic), and activation pathways.

  From baseline (week 0) to week 12

Study Arms (2)

Bariticinib

EXPERIMENTAL

Participants will take one capsule containing 2 mg of baricitinib, once daily, oral administration for 12 weeks

Drug: Bariticinib 2 mg

Placebo

PLACEBO COMPARATOR

Participants will take one capsule containing inert substance (maltodextrine), once daily, oral administration for 12 weeks.

Other: Placebo

Interventions

Bariticinib 2 mg DRUG

Commercially available tablets containing 2 mg of barticiinib will be used. The tablets will be re-capsulated to keep the study blind.

Bariticinib

Placebo OTHER

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

Placebo

Eligibility Criteria

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

You may qualify if:

• Males and females aged between 18 and 65 years on the day of screening visit.
• Confirmed HIV-1 infection.
• Receiving suppressive cART for at least 2 years (defined as maintained plasma viral load \<50 copies/mL, allowing for isolated blips \[\<200 cop/ml, non-consecutive, representing \<20% total determinations\]).
• Being on the same cART regimen within at least 4 weeks prior to baseline visit (week 0).
• Willing and able to be adherent to their cART 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 clinical 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 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.
• If female of childbearing potential, willing to undergo urine pregnancy tests at the designated time points.
• If positive IgG for varicella zoster, adequate herpes zoster vaccination at least 4 weeks prior to week 0 visit.
• Willing to accept blood draws at time points specified in the Schedule of Events.

You may not qualify if:

• If female of childbearing potential, pregnant or planning a pregnancy during the entire study or lactating.
• 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:
• 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).
• 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).
• 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.
• 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).
• Current use of combined hormonal contraceptives or substitutive hormonal treatment.
• 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.

Sponsors & Collaborators

• 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: lead

Study Sites (1)

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

Badalona, Barcelona, 08916, Spain

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Bariticinib will be re-encapsulated with identical weight and appearance (shape, size, colour and flavour) as the placebo-containing capsules.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized 2:1 to the 2 arms: Bariticinib arm VS Placebo arm

Study Record Dates

• First Submitted: June 11, 2025
• First Posted: June 19, 2025
• Study Start: September 22, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)