Randomized Study of Tolebrutinib Versus Rituximab in Adults with Multiple Sclerosis

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What is this study about?

In this trial, people with Multiple Sclerosis are studied. The study compares an oral medication called Tolebrutinib, taken as a film‑coated tablet, with an intravenous infusion of Rituximab, a drug given through a vein. Both medicines are used to affect the immune system that attacks the nervous system in this disease.

The main aim is to see how the level of a protein called neurofilament light chain in the cerebral spinal fluid changes over time when patients switch from Rituximab to Tolebrutinib compared with staying on Rituximab. Neurofilament light chain is a substance that can rise when nerve fibers are damaged, so measuring it helps understand disease activity.

Participants will be assigned to either continue receiving Rituximab or start taking Tolebrutinib, and they will be followed for up to two years. During this period, regular clinic visits will include blood draws, occasional spinal fluid collection, and standard brain scans to monitor any changes. The study does not involve any experimental procedures beyond the approved medications and routine testing.

1 baseline visit

after joining the trial, the first appointment includes a clinical examination to confirm the diagnosis of multiple sclerosis.

samples of blood and cerebral spinal fluid (csf) are collected, and magnetic resonance imaging is performed to document the condition at the start of the study.

2 initial rituximab infusion

the patient receives an intravenous infusion of rituximab at a dose of 500 mg.

the infusion is administered in a clinical setting and takes several hours to complete.

3 randomization

following the initial infusion, the patient is randomly assigned to one of two groups:

the first group continues treatment with rituximab, and the second group switches to oral tolebrutinib.

4 medication period – tolebrutinib arm

patients assigned to the tolebrutinib arm take a film‑coated tablet containing 60 mg of tolebrutinib once each day.

the daily dose is continued for at least twelve months, with the aim of evaluating changes in csf biomarkers.

5 medication period – rituximab arm

patients who remain on rituximab receive additional intravenous infusions of 500 mg according to the standard schedule used in clinical practice, typically every six months.

these infusions continue for the same twelve‑month observation period as the tolebrutinib arm.

6 scheduled follow‑up visits

at months 3, 6, 12 and 24, the patient attends clinic visits for safety monitoring and sample collection.

blood is drawn to measure serum neurofilament light chain (nfl) and other biomarkers; at months 12 and 24, a repeat csf collection is performed to assess changes in csf nfl, glial fibrillary acidic protein (gfap), and additional exploratory markers.

magnetic resonance imaging may be repeated to document any structural changes in the brain.

7 final assessment

after twenty‑four months, the study concludes with a comprehensive evaluation that includes clinical assessment, imaging, and laboratory measurements.

the data collected are used to compare the effect of tolebrutinib after rituximab with continued rituximab treatment on disease‑related biomarkers.

Who Can Join the Study?

You have signed a written informed consent form agreeing to join the study (this means you understand the study and agree to take part).
You are willing and able to follow all study procedures and assessments as described in the study plan.
If you are a woman who could become pregnant or a man who could father a child, you must agree to use a highly effective birth control method during the study and for at least five months after the last dose.
You have a current diagnosis of Multiple Sclerosis that meets the standard McDonald 2017 criteria (the guidelines doctors use to confirm MS).
You have been treated with the medication rituximab for at least 24 months before the screening visit, and your most recent dose was given between 3 and 9 months before screening.
Your score on the Expanded Disability Status Scale (EDSS) is between 2 and 6 inclusive at the screening visit (EDSS measures disability level in MS, with higher numbers indicating more disability).
You have shown recent worsening in at least one neurological area, such as walking ability, thinking skills, need for walking aids, or bladder/bowel problems, as judged by doctors over the past year.
You are at least 18 years old.
You have not used any other disease‑modifying therapies (DMTs) besides rituximab in the past 24 months.
You have no medical reasons that would prevent you from having the required biomarker tests, which include MRI scans, blood/serum collection, and cerebrospinal fluid (CSF) collection.
You agree to undergo up to three lumbar punctures (a procedure that collects a small amount of CSF from the spine).

Who Cannot Join the Study?

Having primary progressive multiple sclerosis (PPMS) instead of the type being studied.
Having a relapse (a flare‑up of symptoms) in the past 12 months or a gadolinium‑enhancing lesion (a sign of active disease on a special MRI scan) at the screening MRI.
Having a serious new neurological problem in the past 12 months, such as a traumatic brain injury.
Having another disease besides MS (for example, myelitis or bilateral optic neuritis) that could better explain your symptoms.
Using certain MS or immune‑modulating medicines within the last 24 months, including interferon beta, glatiramer acetate, IV immunoglobulin, dimethyl fumarate, teriflunomide, natalizumab, ocrelizumab, ofatumumab, fingolimod, siponimod, ozanimod, anticytokine therapy, plasmapheresis, azathioprine, mitoxantrone, cladribine, cyclophosphamide, any experimental drug not cleared for at least 5 drug half‑lives or 24 months, and any BTK inhibitors.
Taking strong inducers or inhibitors of the liver enzymes cytochrome P450 3A (CYP3A) or strong inhibitors of CYP2C8, which can affect how other medicines work.
Taking any blood‑thinning medicines (anticoagulants or antiplatelet drugs).
Having a low white‑blood‑cell count classified as CTCAE Grade 2 or higher lymphopenia (a safety rating that means the count is noticeably low).
Having another serious illness that could affect participation, such as significant heart, kidney, liver, or metabolic disease, or any unstable medical condition.
Having any major medical or psychiatric disorder that would make it hard to follow the study requirements.
Having a history of serious heart disease, such as uncontrolled cardiac dysrhythmia or arrhythmia (irregular heartbeat), uncontrolled angina pectoris (chest pain), cardiomyopathy (heart muscle disease), or uncontrolled congestive heart failure (severe heart weakness, classified as NYHA class 3 or 4), or having significant findings on an ECG (heart tracing test) at screening.
Having a history of a bleeding problem or known platelet dysfunction, or having a platelet count lower than 150,000 per microliter at screening.
Having a history of significant liver disease or abnormal liver blood tests, such as AST or ALT more than 1.5 times the normal range, conjugated bilirubin more than 1.5 times normal, alkaline phosphatase (AP) more than 2 times normal, or GGT more than 3 times normal, unless these results are explained by a non‑liver cause.
Having active cancer diagnosed within the past 5 years.
Being pregnant or breastfeeding.
Being unable to have an MRI scan (magnetic resonance imaging).
Being unable to follow study instructions or complete study assessments.
Having limited legal capacity (for example, being unable to give legal consent).
Having a history of, or a positive test for, viral hepatitis B that is not explained by vaccination.
Having a history of, or a positive test for, viral hepatitis C or HIV (human immunodeficiency virus) at any time.
Having a positive pregnancy test at the time of screening.

Where you can join this trial?

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Other Sites

Site Name	City	Country	Status
Region Stockholm – SLSO	Stockholm	Sweden

Trial status

Country	Status	Recruitment Start
Sweden	Not yet recruiting	30.04.2026

Trial locations

Investigated drugs:

Tolebrutinib is an oral tablet that blocks a protein called Bruton’s tyrosine kinase (BTK). By inhibiting this protein, the drug can reduce immune activity that contributes to the damage seen in multiple sclerosis. In the study, participants switch to tolebrutinib after receiving rituximab, and researchers will measure how this change affects a fluid marker of nerve injury in the spinal fluid.

Rituximab is given through an IV infusion and works by removing certain immune cells called B‑cells that are involved in the inflammation of multiple sclerosis. In this trial, rituximab is used as the standard treatment that patients have been receiving. Some participants stay on rituximab, while others switch to tolebrutinib, allowing the study to compare the two therapies.

Investigated diseases:

Multiple sclerosis

Multiple Sclerosis – Multiple Sclerosis is a disease of the brain and spinal cord where the protective covering of nerve fibers is damaged. This damage slows or blocks the signals that travel between the brain and the rest of the body. Over time, people may notice increasing difficulty with walking, balance, and coordination. Vision problems, muscle weakness, and numbness can also appear and may come and go at first. As the condition continues, symptoms often become more persistent and affect daily activities.

Trial ID:

2025-523892-50-00

Protocol code:

MSBenefiT

Trial Phase:

Therapeutic confirmatory (Phase III)

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Randomized Study of Tolebrutinib Versus Rituximab in Adults with Multiple Sclerosis

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?