Multiple SclerosisPhase 1/2NCT04025554
Anakinra for the Treatment of Chronically Inflamed White Matter Lesions in Multiple Sclerosis
A Phase 1/2 study testing Anakinra in people with Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Anakinra
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Oct 2019to 24 Oct 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Multiple Sclerosis
- Being tested
- Anakinra
- Keywords
- Chronic Active Lesions, Ultra-high-field (7T) MRI, Interleukin-1 (IL-1), White Matter, Paramagnetic Rim
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnakinraDrug
100 mg daily weeks 1-4, 200 mg daily weeks 5-8, 300 mg daily weeks 9-12.
| Study group | Role | What they receive |
|---|---|---|
| 1/Active treatment | Experimental | Patients with MS will be assigned to the same intervention Receives: Drug: Anakinra |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modulation of One or All Paramagnetic Rim Lesions
Proportion of lesions in which the paramagnetic rim has been modulated at the end of the dosing period.
Measured: 24 weeks
Secondary outcomes (6)
Change in the 9-hole Peg Test (9HPT)
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.
Measured: 24 weeks
Change in the Symbol Digit Modalities Test (SDMT)
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.
Measured: 24 weeks
Change in the Expanded Disability Status Scale (EDSS)
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.
Measured: 24 weeks
Change in Paramagnetic Rim Lesion at Any Time Point
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).
Measured: Up to 24 weeks
Change in Size of Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions
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.
Measured: 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
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.
Measured: Every 4 weeks for the duration of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2019
- Study start25 Oct 2019
- Primary completion24 Oct 2023
- Study completion24 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Daniel S Reich, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04025554
- Sponsor's protocol ID
- 190124
- Other IDs
- 19-N-0124
- Status last verified
- 25 Oct 2023
- First submitted
- 18 Jul 2019
- Last updated
- 27 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anakinra for the Treatment of Chronically Inflamed White Matter Lesions in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT04025554
- Acronym / sponsor ID
- 190124
- Conditions
- Multiple Sclerosis
- Keywords
- Chronic Active Lesions, Ultra-high-field (7T) MRI, Interleukin-1 (IL-1), White Matter, Paramagnetic Rim
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 25 Oct 2019 (actual)
- Primary completion
- 24 Oct 2023 (actual)
- Study completion
- 24 Oct 2023 (actual)
- First posted
- 19 Jul 2019 (actual)
- Results
- Posted 27 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1/Active treatment | Experimental | Drug: AnakinraPatients with MS will be assigned to the same intervention |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anakinra100 mg daily weeks 1-4, 200 mg daily weeks 5-8, 300 mg daily weeks 9-12. | Drug | 1/Active treatment |
Primary outcome
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.
6 secondary outcomes
Change in the 9-hole Peg Test (9HPT)
Time frame: 24 weeks
Change in the Symbol Digit Modalities Test (SDMT)
Time frame: 24 weeks
Change in the Expanded Disability Status Scale (EDSS)
Time frame: 24 weeks
Change in Paramagnetic Rim Lesion at Any Time Point
Time frame: 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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel S Reich, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Anakinra in people with Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site 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 6 inclusion and 21 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: finished, as of the sponsor's last update on 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Modulation of One or All Paramagnetic Rim Lesions (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Dec 2024.