Secondary-progressive Multiple SclerosisPhase 2/3NCT04925557
Study to Assess the Efficacy of Mayzent on Microglia in Secondary Progressive Multiple Sclerosis
A Phase 2/3 study testing Mayzent and Ocrevus in people with Secondary-progressive Multiple Sclerosis, run by State University of New York at Buffalo at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Secondary-progressive Multiple Sclerosis
- What is being tested?
- Mayzent and Ocrevus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Nov 2021to 5 Aug 2023
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University at Buffalo, Buffalo General Hospital
Buffalo, New York, 14203
About this study
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
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.
Read the 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
- Being tested
- Mayzent, Ocrevus
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MayzentDrug
PET imaging to evaluate the effects of Mayzent on the microglia of the brain.
OcrevusDrug
PET imaging to evaluate the effects of Ocrevus on the microglia of the brain.
| Study group | Role | What they receive |
|---|---|---|
| Ocrevus | Active comparator | Patients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Ocrevus by their neurologist. Receives: Drug: Ocrevus |
| Mayzent | Active comparator | Patients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Mayzent by their neurologist. Receives: Drug: Mayzent |
What is being measured
The primary outcome is the main question the study is designed to answer.
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;
Measured: 12 months
Secondary outcomes (2)
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
Measured: 6, 12, 24 and 36 months
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.
Measured: 6, 12, 24 and 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2021
- Study start13 Nov 2021
- Primary completion1 Jun 2023
- Study completion5 Aug 2023
Why it stopped: Lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Secondary-progressive Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by State University of New York at BuffaloThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- State University of New York at Buffalo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Zivadinov, MD, PhD, State University of New York at Buffalo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04925557
- Sponsor's protocol ID
- 00003884
- Status last verified
- Apr 2025
- First submitted
- 24 May 2021
- Last updated
- 13 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04925557
- Acronym / sponsor ID
- 00003884
- Conditions
- Secondary-progressive Multiple Sclerosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment
- Enrolment
- 8 participants (actual)
- Lead sponsor
- State University of New York at BuffaloUniversity, hospital or other
- Study start
- 13 Nov 2021 (actual)
- Primary completion
- 1 Jun 2023 (actual)
- Study completion
- 5 Aug 2023 (actual)
- First posted
- 14 Jun 2021 (actual)
- Results
- Posted 13 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ocrevus | Active comparator | Drug: OcrevusPatients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Ocrevus by their neurologist. |
| Mayzent | Active comparator | Drug: MayzentPatients diagnosed with secondary-progressive multiple sclerosis who have been prescribed Mayzent by their neurologist. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MayzentPET imaging to evaluate the effects of Mayzent on the microglia of the brain. | Drug | Mayzent |
| OcrevusPET imaging to evaluate the effects of Ocrevus on the microglia of the brain. | Drug | Ocrevus |
Primary outcome
Change From Baseline in PET Activation at 12 Months
Time frame: 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;
2 secondary outcomes
Change From Baseline in PET Activation at 6,12,24 and 36 Months Between Mayzent and Active Comparator
Time frame: 6, 12, 24 and 36 months
Number of New Ultrasmall Superparamagnetic Iron Oxide Particles
Time frame: 6, 12, 24 and 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Mayzent and Ocrevus in people with Secondary-progressive Multiple Sclerosis, run by State University of New York at Buffalo at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in PET Activation at 12 Months (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2025.