Open-label, Single-blind, Observational, Comparative, Prospective, 36-month, Longitudinal, Controlled Study to Assess Efficacy of Siponimod (Mayzent®) on Microglia in Patients With Active Secondary Progressive Forms of Multiple Sclerosis

00003884

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.

2021-11-13

2023-06-01

2023-08-05

Completed

Early phase I

18

Inclusion Criteria: * Patients diagnosed with active SPMS according to the Lublin 2014 criteria. Activity is determined by MRI activity (contrast-enhancing lesions; new and unequivocally enlarging T2 lesions) and/or clinical relapses in the 24 months prior to the study baseline. If the clinical MRI is not available to determine the activity (contrast-enhancing lesions; new and unequivocally enlarging T2 lesions), then a screening MRI will be offered to the subjects to determine inclusion/exclusion criteria eligibility. * 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 * None of the exclusion criteria Exclusion Criteria: * 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

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2023-08-14