Study to Assess the Efficacy of Mayzent on Microglia in Secondary Progressive Multiple Sclerosis

NCT ID: NCT04925557

Last Updated: 2025-05-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-13
• Study Completion Date: 2023-08-05

Brief Summary

To assess the efficacy of Mayzent on microglia pathology in patients with active SPMS, as compared to the active control group of MS patients treated with the Ocrevus, as measured by changes in microglial activation in the lesional and non-lesional NAWM and NAGM and in the peri-plaque area of chronic lesions in the brain.

Detailed Description

Multiple sclerosis (MS) is primarily a demyelinating disease of the central nervous system (CNS), but many patients also undergo progressive atrophy, especially in the gray matter (GM). GM atrophy plays a particularly prominent role in development of cognitive and physical disability in MS. Evidence is mounting that there is a profound infiltration of activated microglia and blood-borne macrophages throughout the lesions, whereas in slowly expanding (smoldering) or chronic active expanding lesions, the microglia and macrophages are concentrated as a dense rim around the lesions. Microglia is also activated, in a more diffuse way, in the white matter (WM) and GM with concomitant axonal degeneration and meningeal inflammation. Thus, chronic activation of microglia has been linked to neurodegeneration in the progressive phase of the disease and development of brain atrophy.

No longitudinal studies in MS examined the association between development of microglia-related pathology in patients treated with siponimod (Mayzent®). This will be the first study to examine the treatment effect of Mayzent on microglia in MS.

Conditions

Secondary-progressive Multiple Sclerosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

Ocrevus

Patients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Ocrevus by their neurologist.

Group Type: ACTIVE_COMPARATOR

Ocrevus

Intervention Type: DRUG

PET imaging to evaluate the effects of Ocrevus on the microglia of the brain.

Mayzent

Patients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Mayzent by their neurologist.

Group Type: ACTIVE_COMPARATOR

Mayzent

Intervention Type: DRUG

PET imaging to evaluate the effects of Mayzent on the microglia of the brain.

Interventions

Mayzent

PET imaging to evaluate the effects of Mayzent on the microglia of the brain.

Intervention Type: DRUG

Ocrevus

PET imaging to evaluate the effects of Ocrevus on the microglia of the brain.

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

• Age between 18 and 60 years
• Have EDSS scores between 3.0 and 6.5
• Treatment naïve to both Mayzent and to Ocrevus
• Not being on S1P modulators or B-cell therapies for the last 9 months
• Subjects starting treatment as part of their clinical routine
• Be willing and able to comply with the study procedures for the duration of the trial
• Have given written informed consent and signed Health Insurance Portability and Accountability Act (HIPAA) authorization before any study-related activities are carried out
• Normal kidney functioning (creatinine clearance >59)
• No known hypersensitivity reactions to contrast agents

• Have received treatment within 30 days prior to enrollment with steroids or any other concomitant immunomodulatory therapies
• Have received an investigational drug or experimental procedure within the past 30 days
• Low affinity (LAB) for the DNA single nucleotide polymorphism (SNP) of the TSPO gene on chromosome 22q13.2, using a TaqMan assay
• A CYP2C9*3/*3 genotype
• Have experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure in the last 6 months
• Presence of Mobitz type II second-degree, third-degree AV block, or sick sinus syndrome, unless patient has a functioning pacemaker
• Patients with active HBV confirmed by positive results for HBsAg and anti-HBV tests
• Conditions that may be associated with iron overload (e.g. hemochromatosis, thalassemia and recent blood transfusions)
• Patients with known hypersensitivity to Feraheme® or any of its components or a history of allergic reaction to any intravenous iron product
• Women who are pregnant, lactating or of childbearing age who do not consent to approved contraceptive use during the study
• Subjects who are scheduled for a routine diagnostic MRI exam in the next 4 weeks
• Other warnings and precautions to Mayzent or Ocrevus treatment according to Prescribing Information (PI) will be examined on an individual basis

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

State University of New York at Buffalo

OTHER

Sponsor Role: lead

Responsible Party

Robert Zivadinov, MD, PhD

Director and Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University at Buffalo, Buffalo General Hospital

Buffalo, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

00003884

Identifier Type: -

Identifier Source: org_study_id