Anakinra for the Treatment of Chronically Inflamed White Matter Lesions in Multiple Sclerosis

December 9, 2024 updated by: National Institute of Neurological Disorders and Stroke (NINDS)

Background:

Multiple sclerosis (MS) is a disease of the central nervous system (CNS). People who have MS may have lesions that form on parts of the CNS, such as the brain. Some of these lesions may be inflamed for a long time. This causes MS to progress. There is no treatment for these lesions. Researchers believe that a drug that decreases inflammation can help.

Objective:

To see if a drug called anakinra can help clear inflammation in MS brain lesions.

Eligibility:

People 18 and older with MS and at least one white matter lesion.

Design:

Participants will be screened with one or more Neuroimmunology Clinic protocols.

Participants will have a medical history and physical exam. They will have blood and urine tests. They will have a lumbar puncture. For this, a needle is inserted between the bones in the back, and cerebrospinal fluid is removed. They will also have an MRI of the brain. The MRI scanner is a cylinder surrounded by a strong magnetic field. Participants will lie on a table that slides in and out of the scanner.

Participants will repeat the above procedures throughout the study.

Participants will get their first dose of anakinra at the clinic. They will administer the rest of the doses themselves, by injection under the skin.

Participants will track their daily dosage electronically or in a written drug diary.

Participants will have 4 visits while taking the drug. At each visit, sharps boxes and empty vials will be collected.

Participants will have 2 follow-up visits after completing treatment.

The study will last 28 weeks.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Objective:

The overall goal of this study is to determine the safety, tolerability, and radiological efficacy of up to 12 weeks of subcutaneous injection of anakinra in people with multiple sclerosis and evidence, by magnetic resonance imaging (MRI), of chronic active (also known as smoldering ) lesions in the white matter.

Study population:

5 people with progressive or stable MS, at least one paramagnetic rim lesion on 7-tesla MRI, and no new white matter lesion formation for at least 3 months or clinical relapse for at least 12 months, will complete the study.

Design:

In this open label, dose escalation study, participants will receive up to 12 weeks of

subcutaneous anakinra with initial dose of 100 mg daily up to a target dose of 300 mg daily. Study visits will occur every 4 weeks while on treatment, with 2 follow-up visits at 4 and 12 weeks after treatment discontinuation.

Outcome measures:

The primary outcome measure is disappearance of one or more paramagnetic rims from white matter lesions identified at baseline. Secondary outcomes include safety and tolerability, clinical and radiological outcomes. Exploratory serological and CSF measures will also be obtained to investigate mechanism of action of anakinra and for biomarker development.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

  • INCLUSION CRITERIA:
  • Age greater than or equal to 18
  • Ability to give informed consent
  • If fertile, agreement to use an effective method of birth control during the study and for up to 3 months after the last dose of the study drug
  • Agreement not to participate in any other interventional study while participating in this protocol
  • Diagnosis of MS, either stable or clinically progressive
  • Prior 7-tesla MRI scan, with high image quality in the judgment of the study neuroradiologist, demonstrating at least one white matter lesion with a paramagnetic rim (41)

EXCLUSION CRITERIA:

  • Pregnancy or current breastfeeding
  • Use of another investigational agent within 1 month of screening
  • Active infection and or neutropenia (ANC < 1000 cells/microliter)
  • History of lymphoma
  • Known hypersensitivity to administration of anakinra
  • Previous treatment with anakinra and/or TNF-receptor inhibitor
  • History of asthma
  • QuantiFERON-TB gold positive
  • Prior treatment with anti-CD20 agent (ocrelizumab, rituximab)
  • Prior treatment with anti-CD52 agent (alemtuzumab)
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial or interfere with participation for the full duration of the trial; or not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Renal dysfunction, as defined by Clinical Center guidelines for administration of gadolinium
  • Liver dysfunction, as indicated by baseline aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 1.5 times the upper limit of normal
  • Clinical relapse in the 12 months prior to dosing
  • New lesion formation (by comparison of screening MRI to a previous MRI of sufficient quality) in the 3 months prior to dosing
  • One or more gadolinium-enhancing lesions on the screening scan
  • Change in disease-modifying therapy in the 6 months prior to dosing
  • Medical contraindication for 7-tesla MRI (including, but not limited to, any non-organic implant or other device such as a cardiac pacemaker or infusion pump or other metallic implants, objects, or body piercings, that are not MRI-compatible or cannot be removed)
  • Psychological contraindication for 7-tesla MRI (e.g., claustrophobia)
  • Contraindication to gadolinium administration.
  • Active neoplastic disease or any medical condition, other than MS, that requires concurrent immunosuppression or immunomodulation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 1/Active treatment
Patients with MS will be assigned to the same intervention
Drug: Anakinra
100 mg daily weeks 1-4, 200 mg daily weeks 5-8, 300 mg daily weeks 9-12.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Modulation of One or All Paramagnetic Rim Lesions
Time Frame: 24 weeks
Proportion of lesions in which the paramagnetic rim has been modulated at the end of the dosing period.
24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in the 9-hole Peg Test (9HPT)
Time Frame: 24 weeks
The Nine-Hole Peg Test (9-HPT) is a standardized, quantitative assessment used to measure finger dexterity. The test is administered by asking the participant to take pegs from a container, one by one, and place them into holes on a board as quickly as possible. Participants must then remove the pegs from the holes, one by one, and replace them back into the container. The test is timed with a lower number suggesting faster finger dexterity and a higher number suggesting slower finger dexterity. The results represent the mean change from baseline to end of dosing.
24 weeks
Change in the Symbol Digit Modalities Test (SDMT)
Time Frame: 24 weeks
The Symbol Digit Modalities Test (SDMT) is a neuropsychological test that assesses cognitive status, including processing speed, visual scanning, tracking, and motor speed. Participants are given a set of nine symbol-digit pairs and a sequence of symbols. They then have 90 seconds to match as many symbols in the sequence to their corresponding numbers as possible. The score is the number of correct substitutions within the 90 second interval, with a maximum of 110. The results represent a change from baseline to the end of dosing.
24 weeks
Change in the Expanded Disability Status Scale (EDSS)
Time Frame: 24 weeks
The EDSS is a tool used to measure the severity of multiple sclerosis (MS). The EDSS is based on a combination of scores from eight functional systems (FS), i.e., Muscle weakness, Balance, Coordination and Tremor, Eye Movements, Speech/Swallowing, Unusual Sensations or Numbness, Bowel and Bladder, Eyesight, and Thinking and Memory, and the Disability Status Scale (DSS). The EDSS is a scale that ranges from 0 to 10, with higher scores indicating greater disability. Scores of 1.0 to 4.5 indicate a high degree of ambulatory ability, while scores of 5.0 to 9.5 indicate a loss of ambulatory ability. The results represent a change from baseline to the end of dosing.
24 weeks
Change in Paramagnetic Rim Lesion at Any Time Point
Time Frame: Up to 24 weeks
Participants underwent 7T MRI during the dosing period and the post-dosing period. The results presented describe the proportion of paramagnetic rim lesions in which the rim was diminished or disappeared during the dosing period (weeks 0-12), during the post-dosing period (weeks 12-24) and during the entire study (weeks 0-24).
Up to 24 weeks
Change in Size of Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions
Time Frame: Every 4 weeks for the duration of the study
Paramagnetic rim lesions are multiple sclerosis plaques showing signs of low-grade, ongoing inflammation on MRI. Participants underwent MRI every 4 weeks and we compared the change in size between the participant's paramagnetic rim lesions (PRL+) and non-paramagnetic rim lesions (PRL-). At each time point, the mean group volume of each PRL+ and PRL- was calculated. The results provided include the group means and confidence limits at each time point for PRL+ and PRL- lesion type.
Every 4 weeks for the duration of the study
Changes in T1 Relaxation Time Within Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions
Time Frame: Every 4 weeks for the duration of the study
Paramagnetic rim lesions are multiple sclerosis plaques showing signs of low-grade, ongoing inflammation on MRI. T1 relaxation time is a measure of brain damage on MRI. Participants underwent MRI every 4 weeks and we compared the change in T1 relaxation time between the participant's paramagnetic rim lesions (PRL+) and non-paramagnetic rim lesions (PRL-) at each time point. The results provided include the group means and confidence limits at each time point for PRL+ and PRL- lesion type.
Every 4 weeks for the duration of the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Daniel S Reich, M.D., National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 25, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 24, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 24, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 18, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 18, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 19, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 25, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 190124
  • 19-N-0124

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

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