What is the mechanism of action of this treatment?

Multiple Sclerosis (MS) treatments generally aim to modulate the immune system to reduce inflammation and prevent immune cells from attacking the myelin sheath. Common treatments include interferon beta, which reduces inflammatory cytokines; glatiramer acetate, which acts as a myelin decoy; and monoclonal antibodies like natalizumab, which block immune cell migration into the central nervous system. Bruton's Tyrosine Kinase (BTK) inhibitors, such as Remibrutinib, specifically target B cells and other immune cells by inhibiting BTK, a key enzyme in the signaling pathways that lead to their activation and proliferation. This targeted approach can potentially reduce the autoimmune response more precisely, leading to fewer side effects and better management of MS symptoms.

What side effects are associated with this type of intervention?

Common treatments for Multiple Sclerosis (MS) include interferon beta, glatiramer acetate, and oral agents like dimethyl fumarate. Interferon beta can cause flu-like symptoms, injection site reactions, and elevated liver enzymes. Glatiramer acetate is associated with injection site reactions and, less commonly, systemic reactions such as chest pain and palpitations. Dimethyl fumarate may cause gastrointestinal issues, flushing, and a decrease in lymphocyte counts. These treatments aim to reduce relapse rates and slow disease progression but come with varying side effect profiles that should be discussed with a healthcare provider.

What prior FDA approvals exist?

The FDA has approved several treatments for Multiple Sclerosis (MS), including disease-modifying therapies (DMTs) such as interferons, glatiramer acetate, and newer oral medications like fingolimod, dimethyl fumarate, and teriflunomide. While Remibrutinib, a Bruton's Tyrosine Kinase (BTK) inhibitor, is still under investigation, other BTK inhibitors like evobrutinib have shown promise in clinical trials for MS. These treatments aim to reduce relapse rates and slow disease progression by modulating the immune response.

What other types of research exist?

Promising novel alternatives to Remibrutinib for Multiple Sclerosis patients include BTK inhibitors like Tolebrutinib and Evobrutinib, which are currently in advanced stages of clinical trials. Additionally, therapies such as Ublituximab, an anti-CD20 monoclonal antibody, and Ponesimod, a selective S1P1 receptor modulator, are also emerging as effective treatments for MS.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Remibrutinib vs Teriflunomide for Multiple Sclerosis (REMODEL-1 Trial)

Phase 3

Recruiting

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

EDSS score of 0 to 5.5 (inclusive)

18 to 55 years of age

Must not have

Hematology parameters at screening: Hemoglobin < 10 g/dl (<100g/L), Platelets < 100000/mm3 (<100 x 109/L), Absolute lymphocyte count < 800/mm3 (<0.8 x 109/L), White blood cells <3 000/mm3 (<3.0 x 109/L), Neutrophils < 1 500/mm3 (<1.5 x 109/L), B-cell count < 50% lower limit of normal (LLN) or total IgG & total IgM < LLN (only required for participants who had a history of receiving B-cell therapies, such as rituximab, ocrelizumab or ofatumumab, prior to screening), History or current diagnosis of significant ECG abnormalities, Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment (prior to randomization), Use of other investigational drugs, Requirement for anticoagulant medication or use of dual anti-platelet therapy, Significant bleeding risk or coagulation disorders, History of gastrointestinal bleeding, Major surgery within 8 weeks prior to screening, History of hypersensitivity to any of the study drugs or excipients, Pregnant or nursing (lactating) female participants, prior to randomization, Women of childbearing potential not using highly effective contraception, Sexually active males not agreeing to use condom, Have received any live or live-attenuated vaccines within 6 weeks of randomization or requirement to receive these vaccinations during study, Use of strong CYP3A4 inhibitors or strong CYP3A4 inducers within two weeks prior to randomization

Participants who have had a splenectomy

Timeline

Screening 3 days

Treatment 30 months

Follow Up 4 weeks

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial compares remibrutinib and teriflunomide in patients with relapsing multiple sclerosis. It aims to find out which medication is more effective and safer. Both drugs work by controlling the immune system to reduce relapses. Teriflunomide is an approved treatment for adults with this condition.

Who is the study for?

Adults aged 18-55 with Relapsing Multiple Sclerosis (RMS) as per the McDonald criteria, an EDSS score of 0 to 5.5, and a recent history of relapses or active lesions are eligible. Exclusions include those with certain cancers, mental health risks, other immune diseases besides MS, substance abuse issues, significant organ disorders or infections, severe allergies to study drugs or components, pregnant/nursing women, and those not using effective contraception.

What is being tested?

The trial is testing the effectiveness and safety of Remibrutinib compared to Teriflunomide in treating RMS. Participants will be randomly assigned to receive either Remibrutinib or Teriflunomide while their health outcomes are monitored.

What are the potential side effects?

Potential side effects for both medications may include liver problems, hair thinning or loss (Teriflunomide), increased risk of infection due to immune system effects (Remibrutinib), gastrointestinal disturbances like nausea or diarrhea, headaches and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My disability level allows me to walk without aid or rest for at least 200 meters.

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I am between 18 and 55 years old.

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My condition meets the 2017 criteria for RMS diagnosis.

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My neurological condition has been stable for the last month.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had my spleen removed.

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My disease has lasted over 10 years and I have little to no disability.

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I have severe kidney problems or high creatinine levels.

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I have a significant brain or nerve condition other than multiple sclerosis.

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I have had Progressive Multifocal Leukoencephalopathy or symptoms like it.

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I have been diagnosed with primary progressive multiple sclerosis.

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I have no history or current treatment for serious liver diseases.

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I do not have any serious ongoing infections.

Timeline

Screening ~ 3 days1 visit

Treatment ~ 30 months18 visits

Follow Up ~ 4 weeks1 visit

Screening ~ 3 days

Treatment ~ 30 months

Follow Up ~4 weeks

This trial's timeline: 3 days for screening, 30 months for treatment, and 4 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Annualized relapse rate (ARR) of confirmed relapses [Core Part]

Secondary study objectives

Annualized rate of new or enlarging T2 lesion [Core Part]

Annualized rate of new or enlarging T2 lesion [Extension Part]

Annualized relapse rate (ARR) of confirmed relapses [Extension Part]

+21 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Group I: Remibrutinib - Extension (on teriflunomide in Core)Experimental Treatment1 Intervention

Participants on teriflunomide in Core will switch to remibrutinib tablet

Group II: Remibrutinib - ExtensionExperimental Treatment1 Intervention

Participants on remibrutinib in Core will continue on remibrutinib tablet

Group III: Remibrutinib - CoreExperimental Treatment1 Intervention

Remibrutinib tablet and matching placebo of teriflunomide capsule

Group IV: Teriflunomide - CoreActive Control1 Intervention

Teriflunomide capsule and matching placebo remibrutinib tablet

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Multiple Sclerosis (MS) treatments generally aim to modulate the immune system to reduce inflammation and prevent immune cells from attacking the myelin sheath. Common treatments include interferon beta, which reduces inflammatory cytokines; glatiramer acetate, which acts as a myelin decoy; and monoclonal antibodies like natalizumab, which block immune cell migration into the central nervous system. Bruton's Tyrosine Kinase (BTK) inhibitors, such as Remibrutinib, specifically target B cells and other immune cells by inhibiting BTK, a key enzyme in the signaling pathways that lead to their activation and proliferation. This targeted approach can potentially reduce the autoimmune response more precisely, leading to fewer side effects and better management of MS symptoms.