- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02527460
Anakinra, A Recombinant Human IL-1 Receptor Antagonist for Neuroinflammation in HIV-1 Infection
Anakinra, a Recombinant Human IL-1 Receptor Antagonist for Neuroinflammation in HIV-1 Infection
Background:
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.
Objective:
To see if a drug for inflammatory diseases is safe for people with HIV-infection on antiretroviral therapy.
Eligibility:
Adults 18-61 years old with HIV who are enrolled in another study.
Design:
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21205
- Johns Hopkins University
-
Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center, 9000 Rockville Pike
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
- INCLUSION CRITERIA
- Age 18-61 years old
- Laboratory-confirmed HIV-1 infection
- CD4 count >350 cells/mm^3
- Plasma HIV RNA <50 copies/mL for at least 12 months prior to screening. Participants who have a viral blip of up to 200 copies/mL may be included if they have a preceding and following VL <50 copies/mL.
- Stable antiretroviral therapy regimen for greater than or equal to 3 months prior to screening
- Weight greater than or equal to 50 kg
- Have participated in NIH protocol 13 N-0149 or the JHU Clinical Outcomes Core
- Completion of at least 7th grade (according to subject report) and ability to speak, read, and understand English to allow use of standard neurocognitive batteries
- An established primary care provider
- Willingness to have blood and CSF samples stored for future research
- Willingness to undergo serial lumbar punctures (LPs) per study schedule
- Willingness to undergo genetic testing
- For women of childbearing potential, willingness to use 2 forms of effective birth control beginning 2 weeks before and continuing until 12 weeks after the start of anakinra. One method must be a condom and the other may be a diaphragm or cervical cap with spermicide, oral contraceptive, implant, contraceptive patch, IUD placed at least 3 months ago or having a male partner who had a vasectomy at least 3 months ago.
EXCLUSION CRITERIA
- Presence of a neurologic condition that would confound study evaluations (eg, multiple sclerosis, Parkinson s disease). Neurologic conditions that would not interfere with study evaluations (eg, migraine, peripheral neuropathy) will be allowed.
- Presence of a condition, other than HAND, associated with cognitive impairment (e.g. untreated severe sleep apnea) at screening
- Presence of HIV-associated dementia as determined through participation in NIH protocol 13-N-0149 or the JHU Clinical Outcomes Core
- Inability to provide informed consent
- Past or current psychiatric illness that may interfere with protocol adherence (eg schizophrenia or bipolar disorder)
- Use of any psychiatric medications unless stable greater than or equal to 3 months at the time of screening
- Current asthma requiring treatment
- History of any AIDS-defining opportunistic infection in the past two years or any history of a CNS opportunistic infection
- History of lymphoma or melanoma
- Any medical condition (eg, congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, severe osteoarthritis) that would make frequent study visits and travel difficult for the participant
- Positive urine drug screen or active abuse of illegal drugs, narcotics or alcohol as determined by the study investigator at the time of screening or at baseline evaluations
- Women who are pregnant or actively seeking to become pregnant
- Women who are breastfeeding
- Use of any systemic immunosuppressive medication, including TNF inhibitors, within five half lives of the drug prior to of screening
- Contraindications to LP including: International Normalized Ratio (INR) >1.5, platelets <100,000/Microlitre, or inability to temporarily discontinue aspirin for 7-10 days and nonsteroidal anti-inflammatory drugs for 3 days prior to LP
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x laboratory upper limit of normal
- Absolute neutrophil count <1000/mm^3 or hemoglobin <10mg/dL
- Estimated glomerular filtration rate <60 mL/min or a history of renal dialysis
- Other laboratory abnormality that would make the study risky for the patient as determined by the study investigator
- Acute or chronic hepatitis C virus infection determined by a detectable VL
- Acute or chronic hepatitis B determined by detectable hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) IgM
- History of tuberculosis (TB), or positive TB test at screening (QuantiFERON or tuberculin skin test)
- Other infection (eg, influenza, urinary tract infection) that would affect response to anakinra, or that would represent a risk of significant infection based upon the known effects of anakinra, and the likely effects of anakinra on this population.
- Receipt of live vaccine within four weeks of starting anakinra or planned within three months after study completion
- Contraindication to MRI including pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, some types of aneurysm clips (metal clips on the wall of a large artery), some types of metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, or shrapnel fragments. Participants who require sedation for claustrophobia during the MRI will not be excluded.
- Known hypersensitivity or contraindication to gadolinium or any component of anakinra
- Participation in a clinical protocol (e.g. anti-inflammatory drug intervention study) which includes an intervention that may affect the results of the current study.
- Any condition that would increase risk to the subject or would interfere with the subject s ability to comply with protocol requirements (e.g. inability to travel to the study site frequently).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Frequency and severity of AEs and SAEs
Time Frame: Day 56, Day 112
|
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
|
Day 56, Day 112
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Changes in neurocognitive and neurobehavioral function after 8 weeks
Time Frame: Day 56, Day 112
|
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
|
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
|
Day 56, Day 112
|
Collaborators and Investigators
Collaborators
Publications and helpful links
General Publications
- Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J, McArthur JC, Collier AC, Evans SR, Ellis RJ. The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS. 2007 Sep 12;21(14):1915-21. doi: 10.1097/QAD.0b013e32828e4e27.
- Simioni S, Cavassini M, Annoni JM, Rimbault Abraham A, Bourquin I, Schiffer V, Calmy A, Chave JP, Giacobini E, Hirschel B, Du Pasquier RA. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS. 2010 Jun 1;24(9):1243-50. doi: 10.1097/QAD.0b013e3283354a7b.
- Andersson LM, Hagberg L, Rosengren L, Fuchs D, Blennow K, Gisslen M. Normalisation of cerebrospinal fluid biomarkers parallels improvement of neurological symptoms following HAART in HIV dementia--case report. BMC Infect Dis. 2006 Sep 15;6:141. doi: 10.1186/1471-2334-6-141.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 150183
- 15-N-0183
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HIV Infections
-
University of MinnesotaWithdrawnHIV Infections | HIV/AIDS | Hiv | AIDS | Aids/Hiv Problem | AIDS and InfectionsUnited States
-
University of California, San DiegoUniversity of California, Los Angeles; University of Southern California; California... and other collaboratorsCompleted
-
National Institute of Allergy and Infectious Diseases...Eunice Kennedy Shriver National Institute of Child Health and Human Development...CompletedHIV Infections | HIV SeronegativityUnited States, Puerto Rico
-
Gérond'ifRecruiting
-
University of California, DavisCompleted
-
University of California, San DiegoNational Center for Complementary and Integrative Health (NCCIH)CompletedHIV PositiveUnited States
-
University of ChicagoUniversity of Athens; National Development and Research Institutes, Inc.Completed
-
HIV Prevention Trials NetworkNational Institute on Drug Abuse (NIDA); National Institute of Allergy and...CompletedHIV PositiveIndonesia, Ukraine, Vietnam
-
University of ZimbabweCompleted
-
Florida International UniversityCompleted
Clinical Trials on Anakinra
-
Virginia Commonwealth UniversityAmerican Heart AssociationCompleted
-
University of AthensCompletedCoronary Artery Disease | Inflammation | Rheumatoid ArthritisGreece
-
Weill Medical College of Cornell UniversitySwedish Orphan BiovitrumWithdrawnCovid19 | Mechanical Ventilation Complication | Cytokine StormUnited States
-
University of North Carolina, Chapel HillNational Heart, Lung, and Blood Institute (NHLBI)Withdrawn
-
University of North Carolina, Chapel HillNational Heart, Lung, and Blood Institute (NHLBI)Withdrawn
-
Virginia Commonwealth UniversityNational Heart, Lung, and Blood Institute (NHLBI)CompletedHeart FailureUnited States
-
National Institute of Neurological Disorders and...CompletedMultiple SclerosisUnited States
-
National Institute of Arthritis and Musculoskeletal...CompletedImmune System Diseases | Autoimmune Connective Tissue DisorderUnited States
-
National Institute of Allergy and Infectious Diseases...TerminatedEczema | Atopic Dermatitis | Allergic Disease | Anakinra | KineretUnited States