Anakinra, A Recombinant Human IL-1 Receptor Antagonist for Neuroinflammation in HIV-1 Infection
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|ClinicalTrials.gov Identifier: NCT02527460|
Recruitment Status : Terminated
First Posted : August 19, 2015
Last Update Posted : November 29, 2019
HIV can sometimes cause HIV-associated neurocognitive disorder, or HAND. HAND is HIV-associated neurocognitive disorder. It can affect memory, thinking, or concentration. It can cause mood changes. HAND may be caused by HIV hiding in the central nervous system then causing inflammation. Researchers want to see if a drug for inflammation (Anakinra) can help people with HIV.
To see if a drug for inflammatory diseases is safe for people with HIV-infection on antiretroviral therapy.
Adults 18-61 years old with HIV who are enrolled in another study.
Participants will be screened with medical history, physical exam, and blood and urine tests.
Participants will have up to 15 study visits over 16 weeks.
At study visit 1, participants will have:
- Screening tests repeated.
- Brain magnetic resonance imaging (MRI) scans. They will lie on a table that slides into a metal cylinder in a strong magnetic field. They will get a dye inserted by a thin plastic tube in a vein.
- Lumbar puncture. The lower back will be numbed. A needle will collect fluid from between bones in the back.
- Tests of memory, thinking, and attention. Participants may also fill out forms and do tasks.
Participants will learn how to inject the study drug. Over 8 weeks, they will give themselves the study drug at home every day. They will do up to 3 injections at once. They will write down their injections and any side effects.
Participants will have 5 weekly visits while taking the study drug. They will answer questions and have blood drawn.
At weeks 8 and 16, they will have a visit that repeats visit 1.
|Condition or disease||Intervention/treatment||Phase|
|HIV Infections Neurologic Disorders||Drug: Anakinra||Phase 1|
Objective: HIV persists as a reservoir in the brain in several different cell types, including macrophages, microglia and astrocytes, and this reservoir persists even when antiretroviral therapy (ART) suppresses the virus in blood. This viral persistence in the CNS is thought to cause neuroinflammation through the release of inflammatory cytokines and chemokines. HIV-infected patients who have evidence of neuroinflammation in CSF are more likely to have cognitive impairment even when the virus is optimally treated with ART. This cognitive impairment, currently named HIV-associated neurocognitive disorder (HAND), affects 20-37% of the HIV-infected and ART-treated population. Without ART, the rates of severe HAND are incredibly high, but in the current era in areas where ART is widely available, the cognitive deficits are often subtle. Despite this reduction in the degree of impairment and fewer cases of overt dementia, patients with HAND have poor medication adherence, problems with decision making, vocational disability, and an overall reduced quality of life compared to HIV-infected patients without cognitive impairment.
This phase 1 study of anakinra will investigate the safety of anakinra in patients with HIV on antiretroviral therapy. Anakinra, an IL-1 receptor antagonist that has broad anti-inflammatory effects, has demonstrated safety and efficacy in two other inflammatory diseases (rheumatoid arthritis and neonatal onset multisystem inflammatory disorder) for which it is FDA-approved. It has not yet been used in patients with HIV infection.
Study Population: The study will be conducted simultaneously at two centers: the NIH Clinical Center and the Johns Hopkins University (JHU) Department of Neurology and will enroll twelve participants with HIV infection on antiretroviral therapy. Approximately half of the patients will be enrolled at each site. The study will not enroll patients with evidence of dementia.
Design: This is a single-arm, open-label study of anakinra. Participants will self-administer daily injections of anakinra for 8 weeks. The dose will be increased over the first four weeks to minimize injection site reactions. Participants will be evaluated prior to the first dose of anakinra, weekly during the first five weeks, at the end of anakinra administration, and after an 8-week follow-up period without anakinra.
Patients enrolled at the NIH will complete all visits there. Patients enrolled at JHU will complete all visits there with the exception of the three study MRI s which will be completed at the NIH.
Outcome Measures: Safety will be assessed throughout the 8 weeks of treatment and during the 8-week followup period. The anti-inflammatory effects of anakinra will be explored through analyses of cerebrospinal fluid and magnetic resonance imaging results before and after treatment.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Anakinra, a Recombinant Human IL-1 Receptor Antagonist for Neuroinflammation in HIV-1 Infection|
|Study Start Date :||August 17, 2015|
|Actual Primary Completion Date :||March 2, 2018|
|Actual Study Completion Date :||March 2, 2018|
- Drug: Anakinra
Participants will self-administer daily subcutaneous injections of anakinra for 8 weeks. The dose will be increased over the first four weeks to minimize injection site reactions. The target dose after four weeks is 300mg daily.
- Frequency and severity of AEs and SAEs [ Time Frame: Day 56, Day 112 ]
- Frequency of increases in HIV viral load to greater than or equal to 500 copies/mL on 2 consecutive measurements [ Time Frame: Day 56, Day 112 ]
- Changes in neurocognitive and neurobehavioral function after 8 weeks [ Time Frame: Day 56, Day 112 ]
- Changes in systemic inflammatory biomarkers in plasma after 8 weeks of anakinra and then 8 weeks later [ Time Frame: Day 56, Day 112 ]
- Changes in CNS inflammatory and injury biomarkers in CSF and on MRI after 8 weeks of anakinra and then 8 weeks later [ Time Frame: Day 56, Day 112 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02527460
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21205|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Avindra Nath, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|