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

NCT07222956 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: RS-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis (MS) - Relapsing-remitting; Multiple Sclerosis (MS) Secondary Progressive; Multiple Sclerosis (MS) Primary Progressive

Keywords

multiple sclerosis; Relapsing; Progressive; Remibrutinib

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (8)

• 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

• Quantitative Lesion Burden

  Baseline to Month 24

Study Arms (1)

Remibrutinib, active administration

EXPERIMENTAL

100 mg remibrutinib, twice daily

Drug: Remibrutinib (Open Label)

Interventions

Remibrutinib (Open Label) DRUG

100 mg remibrutinib, twice daily

Remibrutinib, active administration

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• To be eligible for the study, participants must meet the following eligibility criteria at the Screening visit:
• Written informed consent signed by participant.
• English-speaking.
• Male and female participants, 18-60 years of age inclusive.
• 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.
• Expanded Disability Status Score (EDSS) of 0 - 6.5, inclusive.
• Adequate vision and motor function to participate in assessment procedures.
• Females participating in the study must meet one the following criteria:
• 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
• 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.
• 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.
• 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.
• Participants should be in reasonably good health and neurologically stable over the last 1 month (no MS relapse in this period).

You may not qualify if:

• 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.
• 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.
• 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.
• 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
• History of severe renal disease or creatinine level above 1.5 x upper limit normal.
• Pregnancy, planned or current.
• History of severe depression or suicidality.
• 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.
• Active clinically significant bacterial, viral, parasitic, or fungal infections, in the judgement of the investigator.
• History of significant central nervous system disease (e.g. stroke, traumatic brain injury, myelopathy, progressive multifocal leukoencepahalopathy).
• History of splenectomy.
• History of active or latent tuberculosis with a positive QuantiFERON, at screening.
• Individuals with a known immunodeficiency syndrome, drug-induced immunodeficiency, hereditary immunodeficiency, or who test positive for Human immunodeficiency virus (HIV) antibody, at screening

Sponsors & Collaborators

• Moein Amin: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis; Recurrence

Interventions

remibrutinib

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Moein Amin, MD, MS

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Planchon, MS, PhD

CONTACT

216-636-1232; planchs@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: investigator-run, open-label

Study Record Dates

• First Submitted: October 23, 2025
• First Posted: October 30, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): October 30, 2030
• Study Completion (Estimated): December 30, 2030
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

US (1)