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

Primary Purpose

Secondary-progressive Multiple Sclerosis

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Mayzent

Ocrevus

About this trial

This is an interventional diagnostic trial for Secondary-progressive Multiple Sclerosis

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University at Buffalo, Buffalo General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Ocrevus

Mayzent

Arm Description

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

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

Outcomes

Primary Outcome Measures

Change from baseline in PET Activation at 12 Months

Change from baseline in PET activation of PBR06 in lesional and non-lesional NAWM and NAGM in the brain of the patients under treatment with Mayzent when 100% of patients reach 12 months;

Secondary Outcome Measures

Change from baseline in PET activation at 6,12,24 and 36 months between Mayzent and active comparator

Change from baseline in PET activation of PBR06 in lesional and non-lesional NAWM and NAGM in the brain of the patients treated with Mayzent and active control group at 6, 12, 24 and 36 months from baseline

Number of new ultrasmall superparamagnetic iron oxide particles

The cumulative number of new ultrasmall superparamagnetic iron oxide (USPIO) particles contrast enhancing (CE) active lesions on T1-weighted images between Mayzent and active control group, as measured at 6, 12, 24 and 36 months from baseline.

Full Information

NCT ID

NCT04925557

First Posted

May 24, 2021

Last Updated

August 9, 2023

Sponsor

State University of New York at Buffalo

1. Study Identification

Unique Protocol Identification Number

NCT04925557

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

November 13, 2021 (Actual)

Primary Completion Date

June 1, 2023 (Actual)

Study Completion Date

August 5, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

State University of New York at Buffalo

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

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

Secondary-progressive Multiple Sclerosis

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Masking Description

Analysts had no knowledge of study drug assignment and if a subject as a patient or HC.

Allocation

Non-Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ocrevus

Arm Type

Active Comparator

Arm Description

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

Arm Title

Mayzent

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Mayzent

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Ocrevus

Intervention Description

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

Primary Outcome Measure Information:

Title

Change from baseline in PET Activation at 12 Months

Description

Change from baseline in PET activation of PBR06 in lesional and non-lesional NAWM and NAGM in the brain of the patients under treatment with Mayzent when 100% of patients reach 12 months;

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Change from baseline in PET activation at 6,12,24 and 36 months between Mayzent and active comparator

Description

Time Frame

6, 12, 24 and 36 months

Title

Number of new ultrasmall superparamagnetic iron oxide particles

Description

Time Frame

6, 12, 24 and 36 months

Other Pre-specified Outcome Measures:

Title

MRI Measures between Mayzent and control-treated groups (PBVC)

Description

Percent brain volume change (PBVC) between baseline and 12, 24, and 36 months

Time Frame

12, 24 and 36 months

Title

MRI Measures between Mayzent and control-treated groups (PCVC)

Description

Percent cortical volume change (PCVC), between baseline and 12, 24, and 36 months

Time Frame

12, 24 and 36 months

Title

MRI Measures between Mayzent and control-treated groups(PTVC)

Description

Percent thalamus volume change (PTVC) between baseline and 12, 24, and 36 months

Time Frame

12, 24 and 36 months

Title

MRI Measures between Mayzent and control-treated groups (QSM)

Description

Quantitative susceptibility mapp (QSM) change between baseline and 12, 24, and 36 months

Time Frame

12, 24 and 36 months

Title

Cumulative number of new gadolinium CE lesions

Description

The cumulative number of new gadolinium CE lesions on T1-weighted images at months 6, 12, 24 and 36 months

Time Frame

6, 12, 24 and 36 months

Title

Cumulative number of new or newly enlarging T2 lesions

Description

The cumulative number of new or newly enlarging hyperintense T2 lesions measured at months 6, 12, 24 and 36 months

Time Frame

6, 12, 24 and 36 months

Title

Absolute change in Hyperintense T2 Lesions volume

Description

The absolute change in hyperintense T2-lesion volume (LV) measured at months 6, 12, 24 and 36 months

Time Frame

6, 12, 24 and 36 months

Title

Absolute change in Hypo-intense T1 Lesions volume

Description

The absolute change in hypo-intense T1-lesion volume (LV) measured at months 6, 12, 24 and 36 months

Time Frame

6, 12, 24 and 36 months

Title

Absolute change in serum neurofilament and glial protein

Description

The absolute change in serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP) at 6, 12, 24 and 36 months

Time Frame

6, 12, 24 and 36 months

Title

Association between imaging and clinical and cognitive outcomes

Description

The association between imaging and clinical and cognitive outcomes, incl. the composite EDSS+SDMT, over 24 and 36 months of the study

Time Frame

24 and 36 months

Title

Number of participants with Treatment related adverse events

Description

Safety of Mayzent and active control group over 12, 24, and 36 months of the study

Time Frame

12, 24, and 36 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

University at Buffalo, Buffalo General Hospital

City

Buffalo

State/Province

New York

ZIP/Postal Code

14203

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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