A Study of Remibrutinib Using MR Imaging in Relapsing or Progressive MS (RemiSeven)

An Open-label, Single-center Study of Remibrutinib Using Ultra High-field (7T) MR Imaging in Relapsing or Progressive MS (RemiSeven)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis (MS) - Relapsing-remitting; Multiple Sclerosis (MS) Primary Progressive; Multiple Sclerosis (MS) Secondary Progressive
• Intervention / Treatment: Drug: Remibrutinib (Open Label)

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sarah Planchon, MS, PhD; Phone Number: 216-636-1232; Email: planchs@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
      • Contact: John Mays; Phone Number: 216-445-6339; Email: maysj1@ccf.org
      • Contact: Bryan Davies, RN; Phone Number: 216-444-5253; Email: daviesb@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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 exclusion criteria exist at the Screening Visit:

1. Concurrent treatment with any disease modifying therapy for MS or systemic immunotherapy for other autoimmune or rheumatological disorders (e.g. rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease) according to study protocol.
2. Ongoing substance abuse (drug or alcohol) or any other factor that may interfere with the participant's ability to cooperate and comply with study procedures.
3. History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer) within the past 5 years regardless of treatment or metastasis status.

4. History of liver disease or liver function abnormalities at baseline including Gilbert syndrome:

   i. Acute or chronic liver disease ii. Cirrhosis iii. Any degree of hepatic impairment (i.e., mild, moderate, or severe) based on Child Pugh classification.

   iv. Untreated hepatitis C or active hepatitis B infection v. Alcohol intake greater than 2 drinks/day for men and greater than 1 drink per day for women vi. Transaminases (i.e., AST or ALT) > 1.5x the upper limit of normal (ULN) vii. Total bilirubin >1.5 x ULN viii. Alkaline phosphatase > 2x ULN unless caused by non-liver related disorder or explained by a stable chronic liver disorder

5. History of severe renal disease or creatinine level above 1.5 x upper limit normal.
6. Pregnancy, planned or current.
7. History of severe depression or suicidality.
8. Hematological abnormalities at screening: hemoglobin < 10 g/dl, platelets < 100000/mm3, absolute lymphocyte count < 800/mm3, white blood cells < 3000/mm3, neutrophils < 1500/mm3, B-cell count < 50% lower limit of normal, total IgG or total IgM < lower limit of normal.
9. Active clinically significant bacterial, viral, parasitic, or fungal infections, in the judgement of the investigator.
10. History of significant central nervous system disease (e.g. stroke, traumatic brain injury, myelopathy, progressive multifocal leukoencepahalopathy).
11. History of splenectomy.
12. History of active or latent tuberculosis with a positive QuantiFERON, at screening.
13. Individuals with a known immunodeficiency syndrome, drug-induced immunodeficiency, hereditary immunodeficiency, or who test positive for Human immunodeficiency virus (HIV) antibody, at screening
14. Clinically significant cardiovascular, renal, hepatic, endocrine, metabolic, hematological, pulmonary, or gastrointestinal disorders that in the investigator's opinion would compromise the safety of the participant or interfere with the interpretation of the study results.
15. History or current diagnosis of ECG abnormalities such as concomitant clinically significant cardiac arrhythmias, history of familial long QT syndrome, cardiac arrhythmias requiring anti-arrhythmic treatment with class Ia or III anti-arrhythmic drugs.
16. Resting QT interval corrected by Fridericia's formula (QTcF) >450 msec (male) or >460 msec (female) prior to screening.
17. Requirement for anticoagulant medication or use of dual anti-platelet therapy. Use of acetylsalicylic acid up to 100 mg/day or clopidogrel up to 75 mg/day, is permitted.
18. Significant bleeding risk or history of clinically significant bleeding disorders.
19. Use of gastric acid modifying agents, such as proton pump inhibitors or H2 antagonists.
20. Use of any strong or moderate inhibitors of CYP3A4 (including clarithromycin, grapefruit, itraconazole, ketoconazole), or strong or moderate inducers of CYP3A4 (including carbamazepine, phenytoin, St John's Wort, primidone, modafinil). Use of BCRP or P-glycoprotein substrates. Use of any herbal/dietary supplements 8 weeks prior to first dose of study drug or during the study period. Concomitant medicines will be examined on a case-by-case basis against the Flockhart Table by study investigator, and if needed, the Medical Monitor, to determine allowability.
21. Live vaccines within 6 weeks prior to screening or requirement to receive these vaccinations at any time during study treatment.
22. Inability to complete MRI with contrast (claustrophobia, pacemaker, cochlear implant, metallic implants incompatible with MR, hypersensitivity to gadolinium-based contrast agent, or severe renal disease).
23. Subjects who score "yes" to items 4 or 5 of the C-SSRS suicidal ideation or any of the items on C-SSRS suicidal behavior section at screening.
24. Other factors that the Investigator determines would place the individual at risk for participation or interfere with interpretation of the results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remibrutinib, active administration; 100 mg remibrutinib, twice daily	Drug: Remibrutinib (Open Label); 100 mg remibrutinib, twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative MRI volumetric measurements	Rate of change in regional brain volumes using 7T MRI over 24 months	Baseline to Month 24
Slowly expanding lesions (SELs)	Prevalence of SELs identified using 7T MRI over 24 months	Baseline to Month 24
Paramagnetic rim lesions (PRLs) -- count	Change in count of PRLs identified using 7T MRI over 24 months	Baseline to Month 24
Paramagnetic rim lesions (PRLs) -- size	Change in size of PRLs identified using 7T MRI over 24 months	Baseline to Month 24
Paramagnetic rim lesions (PRLs) -- quantitative susceptibility measures	Change in quantitative susceptibility measures of PRLs identified using 7T MRI over 24 months	Baseline to Month 24
Myelin Water Fraction	Rate of change in myelin water fraction assessed using 7T MRI over 24 months	Baseline to Month 24
Functional MRI (Default mode network)	Functional MRI changes (default mode network) assessed using 7T MRI over 24 months	Baseline to Month 24
Microstructural tissue integrity	Rate of change in microstructural tissue integrity assessed using 7T MRI over 24 months	Baseline to Month 24
Leptomeningeal enhancement	Prevalence of leptomeningeal enhancement identified using 7T MRI over 24 months	Baseline to Month 24
Neuromelanin	Prevalence of regional neuromelanin changes identified using 7T MRI over 24 months	Baseline to Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Change in number of Gadolinium enhancing lesions over 24 months	Baseline to Month 24
Quantitative Lesion Burden	Change in the volume of brain lesions identified over 24 months	Baseline to Month 24
Annualized Relapse Rate (ARR)		Baseline to Month 24
Expanded Disability Status Scale (EDSS)	A scale from 0 to 10. An increase in EDSS score is indicative of an increase in disability	Baseline to Month 24
Serum Neurofilament Light Chain (NfL)		Baseline to Month 24

Collaborators and Investigators

• Sponsor: Moein Amin
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Moein Amin, MD, MS, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): October 30, 2030
• Study Completion (Estimated): December 30, 2030

Study Registration Dates

• First Submitted: October 23, 2025
• First Submitted That Met QC Criteria: October 28, 2025
• First Posted (Actual): October 30, 2025

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: multiple sclerosis; Progressive; Relapsing; Remibrutinib
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Multiple Sclerosis; Recurrence; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; remibrutinib
• Other Study ID Numbers: CCF 25-1070

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No