Baricitinib for HIV/AIDS

Recruiting at 2 trial locations

Overseen By Howard Pope

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: William Tyor

Must be taking: Antiretrovirals

Must not be taking: Immunosuppressives, Anticoagulants

Disqualifiers: Age, Pregnancy, Cardiovascular, Infections, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 10 weeks

95 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether baricitinib, a drug typically used for arthritis, can reduce HIV in the brain. Researchers believe the brain serves as a hidden reservoir, allowing HIV to persist despite treatment. Participants with well-controlled HIV may qualify if they maintain stable health with standard HIV treatments. The trial compares baricitinib to a placebo to determine its effectiveness in decreasing HIV presence in the brain and improving brain health. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in HIV treatment.

Will I have to stop taking my current medications?

The trial requires that participants stop taking immunosuppressive medications and anticoagulants (except aspirin) at least one month before joining. If you are on these medications, you will need to stop them to participate.

Is there any evidence suggesting that baricitinib is likely to be safe for humans?

Research shows that baricitinib is generally safe for use. Previous studies, particularly those involving patients with rheumatoid arthritis, found its side effects similar to those of other treatments.

Some side effects, such as infections, occur more frequently in older adults (65 and up), while younger individuals usually experience fewer issues. The FDA has already approved baricitinib for treating rheumatoid arthritis, indicating confidence in its safety for that condition. This approval also offers reassurance about its safety as researchers explore its use for HIV treatment.

It's important to remember that reactions to the medication can vary. The clinical trial will closely monitor safety, with regular check-ins for participants to watch for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for HIV?

Baricitinib is unique because it offers a different approach to managing HIV. Unlike standard antiretroviral therapies that primarily work to suppress the virus, baricitinib is a JAK inhibitor that targets inflammation pathways, which could help reduce the chronic inflammation associated with HIV. Researchers are excited about baricitinib because it may address some of the long-term health complications in people with well-controlled HIV, potentially improving quality of life beyond what current treatments offer.

What evidence suggests that baricitinib might be an effective treatment for HIV?

Research shows that baricitinib, which participants in this trial may receive, can enter the brain and reduce HIV hiding there. This is important because the brain can harbor HIV and cause issues, even with treatment. An earlier study found that baricitinib lowered HIV levels in the brain and spinal cord. This suggests it might help manage HIV in the brain, a significant challenge with current treatments. Baricitinib is already used to treat rheumatoid arthritis, providing some knowledge about its safety and effects in people. ^{1 4 6 7 8}

Who Is on the Research Team?

William Tyor, MD

Principal Investigator

Professor

Are You a Good Fit for This Trial?

This trial is for adults with HIV/AIDS who have been on antiretroviral therapy (ART) with undetectable viral loads for at least a year and have CD4+ counts over 350. Women must use contraception or be postmenopausal. Exclusions include those under 18 or over 65, history of blood clots, stroke, heart failure, liver cirrhosis, recent serious infections including COVID-19, certain cancers, major surgery within the last two months or planned during the study.

Inclusion Criteria

Current CD4+ > 350 cells/microliter for at least twelve months (on at least two previous clinic visits and confirmed at screening)

Women of reproductive age will have a negative pregnancy test at study entry and agree to contraception while on 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

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)

Exclusion Criteria

You have a history of blood clots in your veins.

You have had a previous stroke.

Pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Baricitinib or placebo for ten weeks to evaluate the change in central nervous system HIV

10 weeks

Follow-up visits at weeks 1, 2, 4, and 10

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Baricitinib

Trial Overview The trial tests Baricitinib's ability to reduce HIV in the central nervous system compared to a placebo. Participants will undergo bloodwork, neurocognitive testing, MRIs and lumbar punctures to assess changes in CNS HIV levels and any improvements in brain function and inflammation markers.

How Is the Trial Designed?

Group I: Baricitinib Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

Baricitinib is already approved in United States, European Union for the following indications:

Approved in United States as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Approved in European Union as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Who Is Running the Clinical Trial?

William Tyor

Lead Sponsor

Trials

1

Recruited

100+

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In a study of 14,049 people living with HIV during 2019-2020, 96% were receiving antiretroviral therapy (ART), indicating a high level of treatment adherence.

The data showed a strong preference for guideline-recommended ART regimens, particularly second-generation integrase strand transfer inhibitors like dolutegravir and bictegravir, along with tenofovir alafenamide, especially among individuals new to ART.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Antiretroviral Treatment Among People With Human Immunodeficiency Virus in the United States: Findings from the Centers for AIDS Research Network of Integrated Clinic Systems Cohort. Ma, J., Nance, RM., Delaney, JAC., et al.[2023]

BMS-663068, an HIV attachment inhibitor, was well tolerated in a Phase IIb trial with 251 treatment-experienced HIV-1-positive subjects, showing no serious adverse events or discontinuations related to the drug.

The safety profile of BMS-663068 was favorable compared to atazanavir/ritonavir, with significantly fewer drug-related adverse events (8.5% vs. 27.5%), indicating its potential as a safe alternative in HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of HIV-1 attachment inhibitor prodrug BMS-663068 in antiretroviral-experienced subjects: week 24 analysis. Lalezari, J., Latiff, GH., Brinson, C., et al.[2018]

65.8% of people living with HIV expressed interest in trying a long-acting regimen (LAR) of cabotegravir and rilpivirine, particularly those with unmet needs such as suboptimal adherence and privacy concerns.

Physicians showed a high willingness to offer LAR in cases of strong medical need and for patients with adherence issues, indicating that this treatment could significantly improve patient quality of life and adherence to HIV therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with interest in a long-acting HIV regimen: perspectives of people living with HIV and healthcare providers in four European countries. Akinwunmi, B., Buchenberger, D., Scherzer, J., et al.[2021]

Baricitinib demonstrated a consistent safety profile over 128 weeks in patients with rheumatoid arthritis, with treatment-emergent adverse events occurring in 63% of patients on 4 mg and 67% on 8 mg, and no unexpected late safety signals identified.

Clinical improvements in disease symptoms were maintained beyond the initial 24-week blinded period, with similar or increased rates of disease improvement observed at weeks 76 and 128, indicating the long-term efficacy of baricitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Baricitinib Through 128 Weeks in an Open-label, Longterm Extension Study in Patients with Rheumatoid Arthritis. Keystone, EC., Genovese, MC., Schlichting, DE., et al.[2021]

BMS-663068, an attachment inhibitor for HIV-1, showed comparable virologic response rates to atazanavir/ritonavir (ATV/r) in treatment-experienced HIV-1-positive subjects, indicating its potential as an effective alternative treatment.

The study, involving 251 participants, demonstrated similar increases in CD4+ T-cell counts across all treatment arms, suggesting that BMS-663068 is as safe and effective as ATV/r in improving immune function in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV-1 attachment inhibitor prodrug BMS-663068 in antiretroviral-experienced subjects: week 24 sub-group analysis. Brinson, C., Lalezari, J., Gulam, LH., et al.[2018]

In a pilot study involving 35 HIV-1-infected patients, the combination of raltegravir with abacavir/lamivudine was effective, with 91% achieving a viral load of less than 50 copies/mL after 48 weeks.

The treatment was generally well-tolerated, with only one patient experiencing virologic failure and a low incidence of treatment-related adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of abacavir/lamivudine and raltegravir in antiretroviral-naïve HIV-1-infected patients: 48-week results of the SHIELD trial. Young, B., Vanig, T., Dejesus, E., et al.[2015]

In a study involving 4731 rheumatoid arthritis patients treated with baricitinib over 24 weeks, 26.57% achieved remission, indicating its effectiveness in real-world clinical practice.

The treatment was associated with a 26.87% incidence of adverse events, including serious infections and other complications, highlighting the need for ongoing safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of baricitinib for rheumatoid arthritis in Japanese clinical practice: 24-week results of all-case post-marketing surveillance. Takagi, M., Atsumi, T., Matsuno, H., et al.[2023]

Baricitinib, a selective JAK1 and JAK2 inhibitor, was found to be safe and well tolerated in healthy volunteers, with no serious treatment-related adverse events reported during the studies.

The drug demonstrated predictable pharmacokinetics, achieving peak plasma concentration within 1.5 hours and showing a dose-linear response, which suggests it could be effective for treating rheumatoid arthritis and other inflammatory disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1/2 inhibitor, in healthy volunteers. Shi, JG., Chen, X., Lee, F., et al.[2021]

A large analysis of adverse event reports revealed that tofacitinib/XR had significantly higher rates of cardiovascular-related (14.1%) and blood clot-related (14.8%) events compared to baricitinib and upadacitinib, indicating potential safety concerns for this medication.

Baricitinib was associated with the highest proportions of death (7.2%) and cancer-related (4.1%) adverse events, suggesting that while all three drugs are in the same class, their safety profiles may differ significantly, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of adverse event reporting of Xeljanz/Xeljanz XR, Olumiant, and Rinvoq to the US Food and Drug Administration. Qian, J., Xue, X., Shannon, J.[2023]

Baricitinib at doses of 4 mg and 8 mg, especially when combined with conventional disease-modifying antirheumatic drugs (cDMARD), showed superior efficacy in treating rheumatoid arthritis compared to placebo, with the 8 mg dose being most effective in the short term and the 4 mg dose in the long term.

However, higher doses of baricitinib (4 mg to 8 mg) were associated with a greater risk of adverse events and infections, highlighting the need for careful monitoring when using these dosages in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of different doses of baricitinib for rheumatoid arthritis: A Bayesian network meta-analysis. Haikun, W., Na, W., Dan, S.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07209267

NCT07209267 | Baricitinib Curative Repression of HIV-1 The goal is to see if baricitinib can safely reduce inflammation and the HIV that is hidden in the body. The study will include adults with HIV ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05452564

NCT05452564 | Baricitinib for Reduction of HIV - 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.

3. withpower.com withpower.com/trial/phase-2-hiv-infections-6-2022-9c5c2

Baricitinib for HIV/AIDS · Recruiting Participants for Phase ... In a study involving 4731 rheumatoid arthritis patients treated with baricitinib over 24 weeks, 26.57% achieved remission, indicating its effectiveness in real ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/418018

Baricitinib for Reduction of HIV - 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.

5. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-baricitinib-in-people-with-hiv/

Study on the Safety and Effects of Baricitinib in People ... The study will help determine if baricitinib can be a safe and effective addition to the current treatment options for people living with HIV-1.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9443639/

A Review of Safety Outcomes from Clinical Trials ... Infections were more frequent in patients aged 65 years or older than in those aged less than 65 years (IR, 5.5/100 PYE vs 2.1/100 PYE) [91] and ...

7. ema.europa.eu ema.europa.eu/en/documents/rmp/olumiant-epar-risk-management-plan_en.pdf

Olumiant, INN-baricitinib - European Medicines Agency To establish the efficacy and safety of baricitinib, trials were conducted first in adults. Safety in patients 2 to less than 18 years of ...

8. ard.bmj.com ard.bmj.com/content/81/3/335

Safety of baricitinib for the treatment of rheumatoid arthritis ... The results suggest that baricitinib has a consistent safety profile as demonstrated in previous reports and is in line with other JAK inhibitors and biologic ...