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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

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

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

17 Sep 2025 → ongoing

Decision date (initial)

2025-05-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Spanish Ministery of Health (Fondo de Investigaciones Sanitarias 2024)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

- To evaluate the safety and tolerability of baricitinib administered at 2 mg once daily during 12 weeks in PWH on suppressive ART.

- To evaluate changes in levels of phosphorylated STAT (pSTAT) in CD4+ T cells, as a pharmacodynamic biomarker of baricitinib activity after 12 weeks of baricitinib 2 mg daily.

Secondary objectives 6

1. To evaluate the effect of baricitinib on proapoptotic pathways mediated by BCL-2 after 12 weeks of baricitinib 2 mg daily.
2. To evaluate the effect of baricitinib on JAK/STAT signaling pathway after 12 weeks of baricitinib 2 mg daily.
3. To evaluate the effect of baricitinib on the HIV-1 reservoir after 12 weeks of baricitinib 2 mg daily.
4. To evaluate the impact of baricitinib on homeostatic cytokines, inflammatory biomarkers and cell death markers after 12 weeks of baricitinib 2 mg daily.
5. To evaluate the effects of baricitinib in immune cell subsets after 12 weeks of baricitinib 2 mg daily.
6. To characterize baricitinib pharmacokinetics in plasma when administered at 2 mg once daily in PWH on suppressive ART.

Conditions and MedDRA coding

Human immunodeficency virus

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Males and females aged between 18 and 65 years on the day of the screening visit.
2. Confirmed HIV-1 infection.
3. 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]).
4. Being on the same cART regimen within at least 4 weeks prior to baseline visit (week 0).
5. Willing and able to be adherent to their cART 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 clinical investigator, the candidate has understood the information provided and can give written Informed Consent.
8. 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.
9. If female of childbearing potential, willing to undergo urine pregnancy tests at the designated time points.
10. If positive IgG for varicella zoster, adequate herpes zoster vaccination at least 4 weeks prior to week 0 visit.
11. Willing to accept blood draws at time points specified in the Schedule of Events.

Exclusion criteria 19

1. If female of childbearing potential, pregnant or planning a pregnancy during the entire study or lactating.
2. Prior history or clinical manifestations of any physical or psychiatric disorder that could impair the subject’s ability to complete the study.
3. Any active AIDS-defining disease or progression of HIV-related disease, except cutaneous Kaposi’s sarcoma not requiring systemic therapy.
4. 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.
5. Systemic treatment for cancer within 1 year of study entry.
6. Known hypersensitivity to any component of the IMP formulation, or severe or multiple allergies to drugs or pharmaceutical agents.
7. 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).
8. Receipt of blood products within 3 months of study entry.
9. 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).
10. 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.
11. 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.)
12. Current use of combined hormonal contraceptives or substitutive hormonal treatment.
13. 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.
14. 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.
15. 15. Positive hepatitis C IgG, unless confirmed clearance of HCV infection (undetectable plasma viral load, spontaneous or following treatment).
16. 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.
17. 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.
18. 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.
19. 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: - eGFR <30 ml/min, - AST > 2.5 x ULN, - ALT > 2.5 x ULN

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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.
2. Levels of pSTAT 1, 3 and 5 in CD4+ T cells, at weeks 0 and 12 measured by Flow cytometry.

Secondary endpoints 6

1. Changes in levels of BCL-2 in CD4+ T cells, at weeks 0 and 12 measured by Flow cytometry.
2. 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.
3. Changes in total and intact proviral HIV-1 DNA (IPDA) in CD4 T cells at weeks 0 and 12.
4. 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.
5. 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.
6. Baricitinib concentrations in plasma at weeks 4 and 12.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

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

Sponsor organisation

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

Address

Carretera Canyet S/n

City

Badalona

Postcode

08916

Country

Spain

Scientific contact point

Organisation

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

Contact name

Jose Moltó

Public contact point

Organisation

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

Contact name

Silvia Gel

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 12 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