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HIV InfectionsPhase 1NCT02527460

Anakinra, A Recombinant Human IL-1 Receptor Antagonist for Neuroinflammation in HIV-1 Infection

A Phase 1 study testing Anakinra in people with HIV Infections and Neurologic Disorders, run by National Institute of Neurological Disorders and Stroke (NINDS) at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 61 years
Conditions the study is for
HIV Infections, Neurologic Disorders
What is being tested?
Anakinra
Type of treatment
Injection or infusion
How many people
1 participants
Where
2 sitesUnited States
Study dates
17 Aug 2015to 2 Mar 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 61 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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.

Who cannot join

  • 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
Show all 28Show fewer
  • 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).

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21205

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: 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.

Read more

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.

Read the 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.

Being tested
Anakinra
Keywords
Inflammation, Cognitive Function, HIV
Medical subject headings
HIV Infections, Nervous System Diseases, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AnakinraDrug

    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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency and severity of AEs and SAEs

    Measured: Day 56, Day 112

  2. Frequency of increases in HIV viral load to greater than or equal to 500 copies/mL on 2 consecutive measurements

    Measured: Day 56, Day 112

Secondary outcomes (3)

  1. Changes in neurocognitive and neurobehavioral function after 8 weeks

    Measured: Day 56, Day 112

  2. Changes in systemic inflammatory biomarkers in plasma after 8 weeks of anakinra and then 8 weeks later

    Measured: Day 56, Day 112

  3. Changes in CNS inflammatory and injury biomarkers in CSF and on MRI after 8 weeks of anakinra and then 8 weeks later

    Measured: Day 56, Day 112

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Aug 2015 (estimated)
  2. Study start17 Aug 2015
  3. Primary completion2 Mar 2018
  4. Study completion2 Mar 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02527460
Sponsor's protocol ID
150183
Other IDs
15-N-0183
Status last verified
2 Mar 2018
First submitted
18 Aug 2015
Last updated
29 Nov 2019
Results posted
No

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.

    PubMed 17721099

  • 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.

    PubMed 19996937

  • 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.

    PubMed 16978408

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Anakinra in people with HIV Infections and Neurologic Disorders, run by National Institute of Neurological Disorders and Stroke (NINDS) at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency and severity of AEs and SAEs (time frame: Day 56, Day 112). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02527460, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2019.

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