Baricitinib for Reduction of HIV - CNS

NCT05452564 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: STUDY000044981R01MH1281582025P012210
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 2

Brief Summary

There is still no cure for the human immunodeficiency virus (HIV). While combination antiretroviral therapy (cART) is effective in decreasing deaths from HIV, infected individuals face a lifetime of treatment and many potential complications including end organ diseases such as HIV-associated neurocognitive disorders. HIV infection is controllable with antiretroviral therapy (ART), but ART cannot eliminate HIV reservoirs. Thus, there is no available cure for HIV. There is a large and growing body of evidence that the central nervous system (CNS) is an HIV reservoir site and a barrier to HIV eradication. Our group has done extensive pre-clinical work with janus-kinase (JAK 1/2) inhibitors. This includes baricitinib, which is an orally available, FDA-approved drug for rheumatoid arthritis. Evidence suggests that this drug has activity against HIV in the central nervous system (CNS). In our recently completed pilot study, we showed that baricitinib crosses the blood brain barrier (BBB) and decreases HIV CNS persistence in the brain. Using bloodwork, neurocognitive testing, MRIs and lumbar punctures, we plan to evaluate the change in central nervous system HIV after treatment with baricitinib versus placebo. We will also evaluate changes in neuroimaging, inflammation in blood and cerebrospinal fluid (CSF), and neuropsychological performance after treatment with baricitinib versus placebo. Evidence shows that the central nervous system is one of the reservoir sites that enables the HIV virus to persist in the body even after years of treatment. In order to attack this reservoir and eventually find a cure, it is vital to learn if certain medications can suppress HIV in the CNS.

Conditions

Human Immunodeficiency Virus

Keywords

Central Nervous System; Cerebrospinal Fluid; Baricitinib

Outcome Measures

Primary Outcomes (1)

• Changes in CSF integrated proviral DNA

  The study team will obtain up to 40 milliliters (ml) of CSF from individuals who weigh at least 60 kilograms, otherwise, they will draw up to 30 ml of CSF. CSF integrated proviral DNA (IPDA and Alu-PCR) will be assessed: Integrated proviral DNA will be performed using existing methods in the clinical research group, which employ the Alu-PCR real-time platform, with a limit of 3 copies. Integrated proviral DNA assay (IPDA) to measure the replication-competent reservoir will be used with digital droplet PCR methodology.

  Baseline and study week 10

Secondary Outcomes (27)

• Changes in CSF HIV RNA by single copy assay

  Baseline and study week 10

• Changes in HIV tat protein in CSF

  Baseline and study week 10

• Changes in CSF HIV cell-associated RNA by Double-R assay.

  Baseline and study week 10

• Changes in CSF HIV cell associated CSF HIV DNA by Double-R assay.

  Baseline and study week 10

• Changes in CSF cell associated DNA

  Baseline and study week 10

Study Arms (2)

Baricitinib

EXPERIMENTAL

Potential participants will be pre-screened through review of the electronic medical record from Emory or Grady. Or if a potential participant receives care elsewhere, a release of medical information form will be signed and sent to the medical center that the individual goes to. The study team will enroll individuals who have well controlled HIV. Participants will then be randomized to either baricitinib or placebo. Patients randomized to Baricitinib group will receive Baricitinib at dose of 2 mg oral for ten weeks. Follow up visits will happen for both groups at weeks 1, 2, 4 and 10.

Drug: Baricitinib 2 MG Oral Tablet

Placebo

PLACEBO COMPARATOR

Potential participants will be pre-screened through review of the electronic medical record from Emory or Grady. Or if a potential participant receives care elsewhere, a release of medical information form will be signed and sent to the medical center that the individual goes to. The study team will enroll individuals who have well controlled HIV. Participants will then be randomized to either baricitinib or placebo. Patients randomized to the placebo group will receive 2 mg oral daily placebo for ten weeks. Follow up visits will happen for both groups at weeks 1, 2, 4 and 10.

Drug: Placebo

Interventions

Baricitinib 2 MG Oral Tablet DRUG

Baricitinib, a Janus Kinase inhibitor drug for viral infections, will be administered orally to subjects randomized to this intervention. The dose will be 2 mg orally for ten weeks. This will be compared with placebo intervention. Follow up visits will take place at week 1,2,4 and 10.

Also known as: Baricitinib

Baricitinib

Placebo DRUG

Patients randomized to the placebo group will receive 2 mg oral daily placebo for ten weeks. Follow up visits will happen for both groups at weeks 1, 2, 4 and 10.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV infected on continuous ART with plasma HIV RNA \<200 copies/ml for at least 12 months (on at least two previous clinic visits and confirmed at screening). If a viral load is documented from a CLIA-certified laboratory 14 days before screening, then this result can be used in place of the screening lab result.
• Current CD4+ \> 350 cells/microliter for at least twelve months (on at least two previous clinic visits and confirmed at screening). If a CD4 count is documented from a CLIA-certified laboratory 30 days before screening, then this result can be used in place of the screening lab result.
• Women of reproductive age will have a negative pregnancy test at study entry and agree to contraception while on the study drug. Women who are at least 50 years of age and who have been amenorrheic for at least 12 months will not be required to agree to contraception to participate.

You may not qualify if:

• \< 18 years of age or \> 65 years of age
• Pregnancy or breastfeeding
• Significant hematological abnormalities at screening (ANC \< 1000, Hgb\<10, platelet\< 100,000)
• History of progressive multifocal leukoencephalopathy
• Untreated latent tuberculosis infection (which will be screened for before entry). If there is a prior positive test, the test does not need to be repeated at screening.
• Immunosuppressive medications (including corticosteroids) and anticoagulants (aspirin acceptable) within 1 month. A partial list is provided in the SOP for staff, but otherwise, if there is a question it will be adjudicated by the Investigator(s).
• History of deep venous thrombosis
• Cardiovascular disease:
• Ever a history of stroke
• Hematologic malignancies including lymphoma and leukemia which have no evidence of cure or are at least in remission for \> 5 years
• Major surgery within 8 weeks before screening or will require major surgery during the study
• Current or recent (\<4 weeks before randomization) clinically serious viral (including COVID-19), a bacterial, fungal, or parasitic infection or any other active or recent infection. History of untreated syphilis infection. If an RPR was negative in the 3 months before screening, then an RPR is not needed at screening
• Symptomatic herpes simplex at the time of randomization
• Symptomatic herpes zoster infection within 12 weeks before randomization.
• History of disseminated/complicated herpes zoster (for example, ophthalmic zoster or CNS involvement).

Sponsors & Collaborators

• William Tyor: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

RECRUITING

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

baricitinib; Tablets

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• William Tyor, MD

  Professor

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Howard Pope

CONTACT

404-616-9786; hpope@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 6, 2022
• First Posted: July 11, 2022
• Study Start: May 18, 2023
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: At the end of the study until 2027
• Access Criteria: Qualified investigators for secondary analyses not related to the primary aims of the study following Emory University guidelines

Locations

US (2)