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Anakinra for the Treatment of Chronically Inflamed White Matter Lesions in Multiple Sclerosis
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Sclerosis | Drug: Anakinra | Phase 1 Phase 2 |
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 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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 10 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Anakinra for the Treatment of Chronically Inflamed White Matter Lesions in Multiple Sclerosis |
| Actual Study Start Date : | October 25, 2019 |
| Estimated Primary Completion Date : | January 31, 2022 |
| Estimated Study Completion Date : | January 31, 2022 |
| Arm | Intervention/treatment |
|---|---|
|
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.
|
- Disappearance of one or all paramagnetic phase rims [ Time Frame: At baseline and every 4 weeks ]Assessment of paramagnetic phase rims by scans.
- Safety and tolerability [ Time Frame: 28 weeks ]Monitoring of AEs
- Expanded Disability Status Scale (EDSS) [ Time Frame: Every 4 weeks for the duarion of study ]Clinical assessment
- 9-hole peg test (9HPT) [ Time Frame: Every 4 weeks for the duarion of study ]Clinical assessment
- Symbol digit modalities test (SDMT) [ Time Frame: Every 4 weeks for the duarion of study ]Clinical assessment
- Proportion of paramagnetic rim lesions in which the rim has diminished or disappeared at any time point [ Time Frame: Every 4 weeks for the duarion of study ]MRI scan
- 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 duarion of study ]MRI scan
- Changes in size of paramagnetic rim lesions at all time points, relative to non-rim lesions [ Time Frame: Every 4 weeks for the duarion of study ]MRI scan
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
- 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
- MRI with gadolinium performed exclusively for research purposes within the past year, except in the context of screening for an interventional trial (MRIs with gadolinium performed in the context of standard of care within the past year are permitted)
- 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
| Contact: Joan M Ohayon, C.R.N.P. | (301) 496-3825 | eatonj@ninds.nih.gov |
| United States, Maryland | |
| National Institutes of Health Clinical Center | Recruiting |
| Bethesda, Maryland, United States, 20892 | |
| Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov | |
| Principal Investigator: | Irene CM Cortese, M.D. | National Institute of Neurological Disorders and Stroke (NINDS) |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | July 18, 2019 | ||||
| First Posted Date ICMJE | July 19, 2019 | ||||
| Last Update Posted Date | April 9, 2021 | ||||
| Actual Study Start Date ICMJE | October 25, 2019 | ||||
| Estimated Primary Completion Date | January 31, 2022 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
Disappearance of one or all paramagnetic phase rims [ Time Frame: At baseline and every 4 weeks ] Assessment of paramagnetic phase rims by scans.
|
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| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
|
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| Original Secondary Outcome Measures ICMJE |
|
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| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Anakinra for the Treatment of Chronically Inflamed White Matter Lesions in Multiple Sclerosis | ||||
| Official Title ICMJE | Anakinra for the Treatment of Chronically Inflamed White Matter Lesions in Multiple Sclerosis | ||||
| Brief 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. 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. |
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| 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 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. |
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| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Phase 1 Phase 2 |
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| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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| Condition ICMJE | Multiple Sclerosis | ||||
| Intervention ICMJE | Drug: Anakinra
100 mg daily weeks 1-4, 200 mg daily weeks 5-8, 300 mg daily weeks 9-12.
|
||||
| Study Arms ICMJE | Experimental: 1/Active treatment
Patients with MS will be assigned to the same intervention
Intervention: Drug: Anakinra
|
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| Publications * | Not Provided | ||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Recruiting | ||||
| Estimated Enrollment ICMJE |
10 | ||||
| Original Estimated Enrollment ICMJE | Same as current | ||||
| Estimated Study Completion Date ICMJE | January 31, 2022 | ||||
| Estimated Primary Completion Date | January 31, 2022 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
EXCLUSION CRITERIA:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | No | ||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | United States | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT04025554 | ||||
| Other Study ID Numbers ICMJE | 190124 19-N-0124 |
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| Has Data Monitoring Committee | Not Provided | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE | Not Provided | ||||
| Responsible Party | National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ) | ||||
| Study Sponsor ICMJE | National Institute of Neurological Disorders and Stroke (NINDS) | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE |
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| PRS Account | National Institutes of Health Clinical Center (CC) | ||||
| Verification Date | April 6, 2021 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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