Baricitinib Curative Repression of HIV-1
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Time to restart ART
研究概览
简要总结
This study is being done to test whether a drug called baricitinib, which blocks specific causes of inflammation, affects HIV-1 viral rebound and viral load levels after HIV treatment is discontinued. Researchers will test the effects of continuing baricitinib in people with HIV before and after discontinuing their antiretroviral therapy. This drug is approved by the Food and Drug Administration (FDA) for other diseases; it is not approved for the treatment of HIV-1. The study team will also investigate any side effects associated with the drug.
详细描述
This study will test whether the medication baricitinib, which reduces inflammation and is already approved for other diseases, can delay the return of HIV after stopping antiretroviral therapy (ART). 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 who have a suppressed viral load on ART.
Participants will receive ART combined with baricitinib for 25 weeks, followed by baricitinib alone after stopping ART. If the virus returns, the previous ART will be restarted. Each participant will be involved in the study for approximately 12 to 18 months.
Blood and other biological samples may be stored for future research use, with the participant's consent.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Documented HIV infection
- •On continuous ART for at least 96 weeks before enrollment, with no interruption of ART for 7 consecutive days or longer in the 48 weeks before enrollment.
- •Plasma HIV-1 RNA levels of <50 copies/mL for at least 96 weeks (a minimum of two measures), and <50 copies/mL for a sample obtained within 90 days before enrollment.
- •CD4+ T-cell count ≥500 cells/mm3 obtained within 90 days prior to enrollment
- •No known history of CD4+ T-cell count nadir <200 cells/mm3
- •Negative pregnancy test at time of study enrollment
- •Additional laboratory criteria apply.
排除标准
- •< 18 years of age or > 70 years of age
- •Pregnancy or breastfeeding, as determined by a blood pregnancy test
- •History of AIDS-defining illness, except for recurrent pneumonia.
- •History of progressive multifocal leukoencephalopathy or clinically significant HIV-associated neurocognitive disease.
- •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.
- •History of use of any immunomodulatory medications within 6 months before enrollment, including systemic corticosteroids (>14 days), immunosuppressants, anti-cancer, interleukins, systemic interferons, systemic chemotherapy, or other medications that the site investigator feels could have an immunomodulatory effect.
- •History of deep venous thrombosis
- •Cardiovascular disease (Coronary artery disease or history of myocardial infarction, Congestive heart failure with left ventricular ejection fraction ≤40% per American Heart Association guidelines, history of stroke)
- •History of HIV-associated malignancy, including Kaposi's sarcoma, or any lymphoma/leukemia or virus-associated cancers. Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or surgery in the preceding 36 months
- •Major surgery within 8 weeks before screening, or will require major surgery during the study
- •Current or recent (<4 weeks before screening) clinically serious viral (including COVID-19), bacterial, fungal, or parasitic infection or any other active or recent infection. History of untreated syphilis infection. If a rapid plasma reagin (RPR) test was negative in the 3 months before screening, then an RPR is not needed at screening
- •Symptomatic herpes simplex at the time of screening.
- •Symptomatic herpes zoster infection within 12 weeks before screening.
- •History of disseminated/complicated herpes zoster (for example, ophthalmic zoster or central nervous system (CNS) involvement).
- •Positive test for hepatitis B virus (HBV)
- •Additional exclusion criteria apply
研究组 & 干预措施
Baricitinib 2mg
Adults with well-controlled HIV on ART will be treated for 25 weeks with baricitinib 2 mg per day orally plus their current ART regimen (Step 1).
Following 25 weeks of baricitinib plus ART, ART will be interrupted, and the participants will be treated with baricitinib alone for up to 25 weeks (Step 2).
If a participant qualifies for ART restart criteria before the end of the maximum 25 weeks of Step 2, they will move to Step 3 early and resume ART, while baricitinib will be discontinued for 25 weeks. Otherwise, participants will remain on baricitinib alone until the end of the 25 weeks of Step 2 and will then resume ART while baricitinib is discontinued for an additional 25 weeks of observation (Step 3).
干预措施: Antiretroviral Therapy (ART) (Drug)
Baricitinib 2mg
Adults with well-controlled HIV on ART will be treated for 25 weeks with baricitinib 2 mg per day orally plus their current ART regimen (Step 1).
Following 25 weeks of baricitinib plus ART, ART will be interrupted, and the participants will be treated with baricitinib alone for up to 25 weeks (Step 2).
If a participant qualifies for ART restart criteria before the end of the maximum 25 weeks of Step 2, they will move to Step 3 early and resume ART, while baricitinib will be discontinued for 25 weeks. Otherwise, participants will remain on baricitinib alone until the end of the 25 weeks of Step 2 and will then resume ART while baricitinib is discontinued for an additional 25 weeks of observation (Step 3).
干预措施: Baricitinib (LY3009104) 2 mg (Drug)
Baricitinib 4mg
Adults with well-controlled HIV on ART will be treated for 25 weeks with baricitinib 4 mg per day orally plus their current ART regimen (Step 1).
Following 25 weeks of baricitinib plus ART, ART will be interrupted, and the participants will be treated with baricitinib alone for up to 25 weeks (Step 2).
If a participant meets the ART restart criteria before the end of the maximum 25 weeks of Step 2, they will advance to Step 3 early and resume ART, while baricitinib will be discontinued for 25 weeks. Otherwise, participants will remain on baricitinib alone until the end of the 25 weeks of Step 2 and will then resume ART while baricitinib is discontinued for an additional 25 weeks of observation (Step 3).
干预措施: Baricitinib (LY3009104) 4 mg (Drug)
Baricitinib 4mg
Adults with well-controlled HIV on ART will be treated for 25 weeks with baricitinib 4 mg per day orally plus their current ART regimen (Step 1).
Following 25 weeks of baricitinib plus ART, ART will be interrupted, and the participants will be treated with baricitinib alone for up to 25 weeks (Step 2).
If a participant meets the ART restart criteria before the end of the maximum 25 weeks of Step 2, they will advance to Step 3 early and resume ART, while baricitinib will be discontinued for 25 weeks. Otherwise, participants will remain on baricitinib alone until the end of the 25 weeks of Step 2 and will then resume ART while baricitinib is discontinued for an additional 25 weeks of observation (Step 3).
干预措施: Antiretroviral Therapy (ART) (Drug)
结局指标
主要结局
Time to restart ART
时间窗: Up to 24 weeks after the baricitinib treatment alone was started
Time to restart ART will be defined by a plasma HIV-1 RNA viral load greater than or equal to 1000 copies/mL following withdrawal of ART during 24 weeks of baricitinib treatment alone (following 26 weeks of baricitinib plus ART).
Number of Participants who discontinued treatment due to adverse events
时间窗: Up to 24 weeks after the start of baricitinib alone was started
Participants who permanently discontinued study drug due to treatment-related adverse events.
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 24 weeks after the start of baricitinib alone was started
Number of participants experiencing treatment-emergent adverse events (TEAEs), including serious adverse events.
Time to restart ART
时间窗: Up to 25 weeks after the baricitinib treatment alone was started
Time to restart ART will be defined by a plasma HIV-1 RNA viral load greater than or equal to 1000 copies/mL following withdrawal of ART during 25 weeks of baricitinib treatment alone (following 25 weeks of baricitinib plus ART).
Number of Participants who discontinued treatment due to adverse events
时间窗: Up to 25 weeks after the start of baricitinib alone was started
Participants who permanently discontinued study drug due to treatment-related adverse events.
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 25 weeks after the start of baricitinib alone was started
Number of participants experiencing treatment-emergent adverse events (TEAEs), including serious adverse events.
次要结局
- Time to a detectable plasma HIV-1 RNA viral load(Up to 24 weeks after baricitinib alone was started.)
- Time to a detectable plasma HIV-1 RNA viral load(Up to 25 weeks after baricitinib alone was started.)
研究者
Vincent Marconi
Professor of Medicine
Emory University