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

NCT04025554 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 19012419-N-0124
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  24 weeks

Secondary Outcomes (6)

• Change in the 9-hole Peg Test (9HPT)

  24 weeks

• Change in the Symbol Digit Modalities Test (SDMT)

  24 weeks

• Change in the Expanded Disability Status Scale (EDSS)

  24 weeks

• Change in Paramagnetic Rim Lesion at Any Time Point

  Up to 24 weeks

• Change in Size of Paramagnetic Rim Lesions at All Time Points, Relative to Non-rim Lesions

  Every 4 weeks for the duration of the study

Study Arms (1)

1/Active treatment

EXPERIMENTAL

Patients with MS will be assigned to the same intervention

Drug: Anakinra

Interventions

Anakinra DRUG

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

1/Active treatment

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Daniel S. Reich
• Organization: National Institutes of Health

reichds@ninds.nih.gov

301-496-1801

Study Officials

• Daniel S Reich, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: July 18, 2019
• First Posted: July 19, 2019
• Study Start: October 25, 2019
• Primary Completion: October 24, 2023
• Study Completion: October 24, 2023
• Last Updated: December 27, 2024
• Results First Posted: December 27, 2024

Record last verified: 2023-10-25

Locations

US (1)