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

NCT02527460 | Terminated Phase 1

• 2 other identifiers: 15018315-N-0183
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

HIV Infections; Neurologic Disorders

Keywords

Inflammation; Cognitive Function; HIV

Outcome Measures

Primary Outcomes (2)

• Frequency and severity of AEs and SAEs

  Day 56, Day 112

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

  Day 56, Day 112

Secondary Outcomes (3)

• Changes in neurocognitive and neurobehavioral function after 8 weeks

  Day 56, Day 112

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

  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

  Day 56, Day 112

Interventions

Anakinra DRUG

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.

Eligibility Criteria

• Age: 18 Years - 61 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead
• Johns Hopkins University: collaborator

Study Sites (2)

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 17721099 BACKGROUND

• 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.

  PMID: 19996937 BACKGROUND

• 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.

  PMID: 16978408 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Nervous System Diseases; Inflammation

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Avindra Nath, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2015
• First Posted: August 19, 2015
• Study Start: August 17, 2015
• Primary Completion: March 2, 2018
• Study Completion: March 2, 2018
• Last Updated: November 29, 2019

Record last verified: 2018-03-02

Locations

US (2)