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Lack of recruitment
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ocrevus | Active Comparator | Patients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Ocrevus by their neurologist. |
|
| Mayzent | Active Comparator | Patients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Mayzent by their neurologist. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mayzent | Drug | PET imaging to evaluate the effects of Mayzent on the microglia of the brain. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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; | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 6, 12, 24 and 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| MRI Measures Between Mayzent and Control-treated Groups (PBVC) | Percent brain volume change (PBVC) between baseline and 12, 24, and 36 months | 12, 24 and 36 months |
| MRI Measures Between Mayzent and Control-treated Groups (PCVC) |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University at Buffalo, Buffalo General Hospital | Buffalo | New York | 14203 | United States |
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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. Patients were recruited from 2 medical clinics.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ocrevus | Patients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Ocrevus by their neurologist. Ocrevus: PET imaging to evaluate the effects of Ocrevus on the microglia of the brain. |
| FG001 | Mayzent | Patients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Mayzent by their neurologist. Mayzent: PET imaging to evaluate the effects of Mayzent on the microglia of the brain. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Patients with relapsing remitting Multiple Sclerosis.
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| ID | Title | Description |
|---|---|---|
| BG000 | Ocrevus | Patients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Ocrevus by their neurologist. Ocrevus: PET imaging to evaluate the effects of Ocrevus on the microglia of the brain. |
| BG001 | Mayzent |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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; | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 12 months |
|
Baseline to 5 months.
Case form provided by the study sponsor.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ocrevus | Patients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Ocrevus by their neurologist. Ocrevus: PET imaging to evaluate the effects of Ocrevus on the microglia of the brain. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Allergic Reaction | Injury, poisoning and procedural complications | Non-systematic Assessment | Fever, chills, headache, numbness in face. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Robert Zivadinov | State University of New York at Buffalo | 716-248-2140 | rzivadinov@bnac.net |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Sep 15, 2023 | Aug 29, 2024 | Prot_SAP_ICF_000.pdf |
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| ID | Term |
|---|---|
| D020528 | Multiple Sclerosis, Chronic Progressive |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C578989 | siponimod |
| C533411 | ocrelizumab |
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Analysts had no knowledge of study drug assignment. .
| Ocrevus |
| Drug |
PET imaging to evaluate the effects of Ocrevus on the microglia of the brain. |
|
| 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. |
| 6, 12, 24 and 36 months |
Percent cortical volume change (PCVC), between baseline and 12, 24, and 36 months
| 12, 24 and 36 months |
| MRI Measures Between Mayzent and Control-treated Groups(PTVC) | Percent thalamus volume change (PTVC) between baseline and 12, 24, and 36 months | 12, 24 and 36 months |
| MRI Measures Between Mayzent and Control-treated Groups (QSM) | Quantitative susceptibility mapp (QSM) change between baseline and 12, 24, and 36 months | 12, 24 and 36 months |
| Cumulative Number of New Gadolinium CE Lesions | The cumulative number of new gadolinium CE lesions on T1-weighted images at months 6, 12, 24 and 36 months | 6, 12, 24 and 36 months |
| Cumulative Number of New or Newly Enlarging T2 Lesions | The cumulative number of new or newly enlarging hyperintense T2 lesions measured at months 6, 12, 24 and 36 months | 6, 12, 24 and 36 months |
| Absolute Change in Hyperintense T2 Lesions Volume | The absolute change in hyperintense T2-lesion volume (LV) measured at months 6, 12, 24 and 36 months | 6, 12, 24 and 36 months |
| Absolute Change in Hypo-intense T1 Lesions Volume | The absolute change in hypo-intense T1-lesion volume (LV) measured at months 6, 12, 24 and 36 months | 6, 12, 24 and 36 months |
| Absolute Change in Serum Neurofilament and Glial Protein | The absolute change in serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP) at 6, 12, 24 and 36 months | 6, 12, 24 and 36 months |
| Association Between Imaging and Clinical and Cognitive Outcomes | The association between imaging and clinical and cognitive outcomes, incl. the composite EDSS+SDMT, over 24 and 36 months of the study | 24 and 36 months |
| Number of Participants With Treatment Related Adverse Events | Safety of Mayzent and active control group over 12, 24, and 36 months of the study | 12, 24, and 36 months |
Patients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Mayzent by their neurologist.
Mayzent: PET imaging to evaluate the effects of Mayzent on the microglia of the brain.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
|
| Secondary | 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 | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 6, 12, 24 and 36 months |
|
|
| Secondary | 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. | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 6, 12, 24 and 36 months |
|
|
| Other Pre-specified | MRI Measures Between Mayzent and Control-treated Groups (PBVC) | Percent brain volume change (PBVC) between baseline and 12, 24, and 36 months | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 12, 24 and 36 months |
|
|
| Other Pre-specified | MRI Measures Between Mayzent and Control-treated Groups (PCVC) | Percent cortical volume change (PCVC), between baseline and 12, 24, and 36 months | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 12, 24 and 36 months |
|
|
| Other Pre-specified | MRI Measures Between Mayzent and Control-treated Groups(PTVC) | Percent thalamus volume change (PTVC) between baseline and 12, 24, and 36 months | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 12, 24 and 36 months |
|
|
| Other Pre-specified | MRI Measures Between Mayzent and Control-treated Groups (QSM) | Quantitative susceptibility mapp (QSM) change between baseline and 12, 24, and 36 months | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 12, 24 and 36 months |
|
|
| Other Pre-specified | Cumulative Number of New Gadolinium CE Lesions | The cumulative number of new gadolinium CE lesions on T1-weighted images at months 6, 12, 24 and 36 months | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 6, 12, 24 and 36 months |
|
|
| Other Pre-specified | Cumulative Number of New or Newly Enlarging T2 Lesions | The cumulative number of new or newly enlarging hyperintense T2 lesions measured at months 6, 12, 24 and 36 months | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 6, 12, 24 and 36 months |
|
|
| Other Pre-specified | Absolute Change in Hyperintense T2 Lesions Volume | The absolute change in hyperintense T2-lesion volume (LV) measured at months 6, 12, 24 and 36 months | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 6, 12, 24 and 36 months |
|
|
| Other Pre-specified | Absolute Change in Hypo-intense T1 Lesions Volume | The absolute change in hypo-intense T1-lesion volume (LV) measured at months 6, 12, 24 and 36 months | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 6, 12, 24 and 36 months |
|
|
| Other Pre-specified | Absolute Change in Serum Neurofilament and Glial Protein | The absolute change in serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP) at 6, 12, 24 and 36 months | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 6, 12, 24 and 36 months |
|
|
| Other Pre-specified | Association Between Imaging and Clinical and Cognitive Outcomes | The association between imaging and clinical and cognitive outcomes, incl. the composite EDSS+SDMT, over 24 and 36 months of the study | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 24 and 36 months |
|
|
| Other Pre-specified | Number of Participants With Treatment Related Adverse Events | Safety of Mayzent and active control group over 12, 24, and 36 months of the study | Study was terminated. No subject had any further data collected after the initial visit. | Posted | 12, 24, and 36 months |
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 0 |
| 5 |
| EG001 | Mayzent | Patients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Mayzent by their neurologist. Mayzent: PET imaging to evaluate the effects of Mayzent on the microglia of the brain. | 0 | 3 | 0 | 3 | 2 | 3 |
|
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| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |