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

Trial Summary

What is the purpose of this trial?

This trial tests if baricitinib, a pill for arthritis, can reduce HIV in the brain. It targets people with HIV on treatment who still have HIV in their brain. The drug works by entering the brain and lowering HIV levels.

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 baricitinib generally safe for humans?

Baricitinib has been generally safe and well tolerated in studies with healthy volunteers and patients with rheumatoid arthritis, with no serious treatment-related adverse events reported in some studies. However, there have been reports of serious adverse events like death and cancer, suggesting that while it is generally safe, there are risks that need to be considered. ^{1 2 3 4 5}

How does the drug Baricitinib differ from other treatments for HIV/AIDS?

Baricitinib is unique because it is primarily known as a treatment for rheumatoid arthritis and works by inhibiting Janus kinase (JAK) enzymes, which are involved in inflammation. This mechanism is different from standard HIV treatments, which typically focus on preventing the virus from replicating or entering cells. ^{6 7 8 9 10}

Research Team

William Tyor, MD

Principal Investigator

Professor

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1/2 inhibitor, in healthy volunteers. [2021]

3. Canada 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of different doses of baricitinib for rheumatoid arthritis: A Bayesian network meta-analysis. [2022]

6. United States 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. [2023]

7. England 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. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Safety profile of HIV-1 attachment inhibitor prodrug BMS-663068 in antiretroviral-experienced subjects: week 24 analysis. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

HIV-1 attachment inhibitor prodrug BMS-663068 in antiretroviral-experienced subjects: week 24 sub-group analysis. [2018]

10. England 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. [2015]