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

Primary Purpose

Multiple Sclerosis

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Anakinra

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Chronic Active Lesions, Ultra-high-field (7T) MRI, Interleukin-1 (IL-1), White Matter, Paramagnetic Rim

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1/Active treatment

Arm Description

Patients with MS will be assigned to the same intervention

Outcomes

Primary Outcome Measures

Disappearance of one or all paramagnetic phase rims

Assessment of paramagnetic phase rims by scans.

Secondary Outcome Measures

Symbol digit modalities test (SDMT)

Clinical assessment

Safety and tolerability

Monitoring of AEs

Proportion of paramagnetic rim lesions in which the rim has diminished or disappeared at any time point

MRI scan

Expanded Disability Status Scale (EDSS)

Clinical assessment

Changes in T1 relaxation time within paramagnetic rim lesions at all time points, relative to non-rim lesions

MRI scan

Changes in size of paramagnetic rim lesions at all time points, relative to non-rim lesions

MRI scan

9-hole peg test (9HPT)

Clinical assessment

Full Information

NCT ID

NCT04025554

First Posted

July 18, 2019

Last Updated

October 14, 2023

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

1. Study Identification

Unique Protocol Identification Number

NCT04025554

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 19, 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 25, 2019 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

Keywords

Chronic Active Lesions, Ultra-high-field (7T) MRI, Interleukin-1 (IL-1), White Matter, Paramagnetic Rim

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

1/Active treatment

Arm Type

Experimental

Arm Description

Patients with MS will be assigned to the same intervention

Intervention Type

Drug

Intervention Name(s)

Anakinra

Intervention Description

100 mg daily weeks 1-4, 200 mg daily weeks 5-8, 300 mg daily weeks 9-12.

Primary Outcome Measure Information:

Title

Disappearance of one or all paramagnetic phase rims

Description

Assessment of paramagnetic phase rims by scans.

Time Frame

At baseline and every 4 weeks

Secondary Outcome Measure Information:

Title

Symbol digit modalities test (SDMT)

Description

Clinical assessment

Time Frame

Every 4 weeks for the duarion of study

Title

Safety and tolerability

Description

Monitoring of AEs

Time Frame

28 weeks

Title

Proportion of paramagnetic rim lesions in which the rim has diminished or disappeared at any time point

Description

MRI scan

Time Frame

Every 4 weeks for the duration of the study

Title

Expanded Disability Status Scale (EDSS)

Description

Clinical assessment

Time Frame

Every 4 weeks for the duarion of study

Title

Changes in T1 relaxation time within paramagnetic rim lesions at all time points, relative to non-rim lesions

Description

MRI scan

Time Frame

Every 4 weeks for the duration of the study

Title

Changes in size of paramagnetic rim lesions at all time points, relative to non-rim lesions

Description

MRI scan

Time Frame

Every 4 weeks for the duration of the study

Title

9-hole peg test (9HPT)

Description

Clinical assessment

Time Frame

Every 4 weeks for the duarion of study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Shari L Sawney

Phone

(301) 496-3825

shari.sawney@nih.gov

First Name & Middle Initial & Last Name or Official Title & Degree

Daniel S Reich, M.D.

Phone

(301) 496-1801

reichds@ninds.nih.gov

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Daniel S Reich, M.D.

Organizational Affiliation

National Institute of Neurological Disorders and Stroke (NINDS)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Phone

800-411-1222

Ext

TTY8664111010

prpl@cc.nih.gov

12. IPD Sharing Statement

Links:

URL

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2019-N-0124.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

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

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