Multiple Sclerosis (MS) Primary Progressive, Multiple Sclerosis (MS) - Relapsing-remitting, Multiple Sclerosis (MS) Secondary Progressive
Conditions
Keywords
multiple sclerosis, Relapsing, Progressive, Remibrutinib
Brief summary
The study is an investigator-run, study following participants for 2 years with twice-daily remibrutinib. MRI is the main endpoint. Safety, tolerability, and efficacy are secondary endpoints. Approximately 20 participants with relapsing or progressive forms of MS will be recruited.
Detailed description
The study is an investigator-run, open-label Phase 2 study with approximately 24 total months of observation, involving approximately 20 participants with relapsing or progressive forms of MS. Participants will be recruited from the patient populations followed at CCF. All participants will take 100 mg remibrutinib twice daily. They will receive 4 MRIs, blood tests, EKGs, physical exams, and clinical functioning exams periodically to assess safety, tolerability, and efficacy of the study drug. All study activities will be performed at the Cleveland Clinic Mellen Center.
Interventions
100 mg remibrutinib, twice daily
Sponsors
Moein Amin
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
investigator-run, open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
To be eligible for the study, participants must meet the following eligibility criteria at the Screening visit: 1. Written informed consent signed by participant. 2. English-speaking. 3. Male and female participants, 18-60 years of age inclusive. 4. Established diagnosis of relapsing or progressive MS, as defined by the 2024 revision of McDonald Diagnostic Criteria (any form of MS). A diagnosis of MS must be confirmed at the time of the screening visit. 5. Expanded Disability Status Score (EDSS) of 0 - 6.5, inclusive. 6. Adequate vision and motor function to participate in assessment procedures. 7. Females participating in the study must meet one the following criteria: 1. Surgically sterilized (e.g., hysterectomy, bilateral oophorectomy or tubal ligation) for at least 6 months or postmenopausal (postmenopausal females must have no menstrual bleeding for at least 1 year) or 2. If not postmenopausal, agree to use a double method of contraception, one of which is a barrier method (e.g., intrauterine device plus condom, spermicidal gel plus condom) 30 days prior to dosing until 30 days after last dose and have negative human chorionic gonadotropin (β-hCG) test for pregnancy at screening and at each follow-up visit. 8. Males who have not had a vasectomy must use appropriate contraception methods (barrier or abstinence) from 30 days prior to dosing until 30 days after last dose. 9. Evidence of disease activity in the prior 12 months (at least one clinical relapse or one gadolinium enhancing lesion or new T2 lesion) or presence of disability worsening based clinician's assessment in the prior 12 months. 10. Participants should be in reasonably good health and neurologically stable over the last 1 month (no MS relapse in this period).
Exclusion criteria
Participants will be excluded from the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Paramagnetic rim lesions (PRLs) -- quantitative susceptibility measures | Baseline to Month 24 | Change in quantitative susceptibility measures of PRLs identified using 7T MRI over 24 months |
| Myelin Water Fraction | Baseline to Month 24 | Rate of change in myelin water fraction assessed using 7T MRI over 24 months |
| Functional MRI (Default mode network) | Baseline to Month 24 | Functional MRI changes (default mode network) assessed using 7T MRI over 24 months |
| Microstructural tissue integrity | Baseline to Month 24 | Rate of change in microstructural tissue integrity assessed using 7T MRI over 24 months |
| Leptomeningeal enhancement | Baseline to Month 24 | Prevalence of leptomeningeal enhancement identified using 7T MRI over 24 months |
| Neuromelanin | Baseline to Month 24 | Prevalence of regional neuromelanin changes identified using 7T MRI over 24 months |
| Quantitative MRI volumetric measurements | Baseline to Month 24 | Rate of change in regional brain volumes using 7T MRI over 24 months |
| Slowly expanding lesions (SELs) | Baseline to Month 24 | Prevalence of SELs identified using 7T MRI over 24 months |
| Paramagnetic rim lesions (PRLs) -- count | Baseline to Month 24 | Change in count of PRLs identified using 7T MRI over 24 months |
| Paramagnetic rim lesions (PRLs) -- size | Baseline to Month 24 | Change in size of PRLs identified using 7T MRI over 24 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantitative Lesion Burden | Baseline to Month 24 | Change in the volume of brain lesions identified over 24 months |
| Annualized Relapse Rate (ARR) | Baseline to Month 24 | — |
| Expanded Disability Status Scale (EDSS) | Baseline to Month 24 | A scale from 0 to 10. An increase in EDSS score is indicative of an increase in disability |
| Serum Neurofilament Light Chain (NfL) | Baseline to Month 24 | — |
| Frequency of Treatment Emergent Adverse Events (TEAEs) | Baseline to Month 24 | — |
| Frequency of Serious Adverse Events (SAEs) | Baseline to Month 24 | — |
| Frequency of study medication discontinuation | Baseline to Month 24 | — |
| Gadolinium Enhancing Lesions | Baseline to Month 24 | Change in number of Gadolinium enhancing lesions over 24 months |
Countries
United States
Contacts
CONTACTSarah Planchon, MS, PhD
PRINCIPAL_INVESTIGATORMoein Amin, MD, MS
The Cleveland Clinic
Outcome results
None listed