What side effects are associated with this type of intervention?

Common treatments for Multiple Sclerosis (MS) include interferon beta-1a, glatiramer acetate, dimethyl fumarate, and teriflunomide. Interferon beta-1a can cause flu-like symptoms, injection site reactions, and liver enzyme abnormalities. Glatiramer acetate may lead to injection site reactions and transient chest pain. Dimethyl fumarate is associated with flushing, gastrointestinal issues, and lymphopenia. Teriflunomide can cause liver toxicity, gastrointestinal disturbances, and hair thinning. While specific side effects of Bruton's Tyrosine Kinase Inhibitors like Remibrutinib are not detailed, they may share common immunomodulatory side effects such as increased risk of infections and potential liver enzyme elevations.

What prior FDA approvals exist?

The FDA has approved several treatments for Multiple Sclerosis (MS), including immunomodulatory and immunosuppressive drugs. Glatiramer acetate, an immunomodulator, is indicated for relapsing forms of MS and has shown efficacy in reducing relapse rates and disability progression. Mitoxantrone, an immunosuppressant, is approved for both relapsing-remitting and progressive forms of MS but is used sparingly due to severe side effects. While the context does not provide specific information on FDA-approved BTK inhibitors for MS, ongoing studies like the one on Remibrutinib suggest a growing interest in this class of drugs for their potential benefits in treating MS.

What other types of research exist?

Promising novel alternatives to Remibrutinib for Multiple Sclerosis patients include: 1) Alemtuzumab, which is effective for highly active relapsing-remitting MS (RRMS) and has shown superior efficacy compared to interferon beta-1a. 2) Ocrelizumab, a monoclonal antibody targeting CD20-positive B cells, effective for both RRMS and primary progressive MS (PPMS). 3) Siponimod, a selective sphingosine-1-phosphate receptor modulator, effective for secondary progressive MS (SPMS). 4) Cladribine, an oral immunosuppressive drug, effective for RRMS and SPMS. These alternatives offer different mechanisms of action and may be suitable based on individual patient profiles and disease characteristics.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Remibrutinib vs Teriflunomide for Multiple Sclerosis (REMODEL-2 Trial)

Q: What is the mechanism of action of this treatment?

Multiple Sclerosis (MS) treatments primarily aim to modulate the immune system to reduce inflammation and prevent further damage to the nervous system. Common treatments include interferon beta, which reduces inflammatory cell migration across the blood-brain barrier, and glatiramer acetate, which shifts the immune response from a pro-inflammatory to an anti-inflammatory state. Oral therapies like dimethyl fumarate and teriflunomide inhibit immune cell activation and proliferation. Bruton's Tyrosine Kinase (BTK) inhibitors, such as Remibrutinib, target B-cell and myeloid cell signaling pathways, potentially reducing the activity of these immune cells in MS. These mechanisms are crucial for MS patients as they help manage relapses, slow disease progression, and improve quality of life by minimizing neurological damage.

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)

Neurologically stable within 1 month

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 use of moderate or strong CYP3A4 inducers within two weeks prior to randomization

Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or Neurological symptoms consistent with PML

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to 30 months

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial compares two medications, remibrutinib and teriflunomide, for treating patients with relapsing multiple sclerosis. These patients have repeated episodes of symptoms and need effective treatments. The medications work by controlling the immune system to prevent it from causing damage to the nervous system. Teriflunomide is an approved medication for adults with relapsing multiple sclerosis.

Who is the study for?

Adults aged 18-55 with Relapsing Multiple Sclerosis (RMS) who've had at least one relapse in the past year or a new lesion. They must be neurologically stable, not have primary progressive MS, no severe CNS diseases other than MS, and no history of certain cancers or infections like PML. Women must use effective contraception; men agree to use condoms.

What is being tested?

The trial is testing the effectiveness and safety of Remibrutinib compared to Teriflunomide in treating RMS. Participants will receive either drug and their health outcomes will be monitored to see which treatment works better for controlling the disease.

What are the potential side effects?

Potential side effects may include liver problems, infection risks due to immune system effects, digestive issues, allergic reactions to medication components, blood disorders such as low platelet counts or anemia, and possibly others depending on individual health conditions.

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 200 meters.

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My neurological condition has been stable for the last month.

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My condition meets the 2017 criteria for RMS diagnosis.

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My condition has worsened at least once in the past year or I have had an active lesion recently.

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I am between 18 and 55 years old.

Exclusion Criteria

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

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I have had Progressive Multifocal Leukoencephalopathy or symptoms like it.

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

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I have had cancer in the past, but it was either skin cancer removed completely or cervical cancer that did not spread.

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I have severe kidney problems or high creatinine levels.

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I have a history of or am currently being treated for liver disease.

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I have been diagnosed with primary progressive multiple sclerosis.

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I do not have any serious ongoing infections.

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I have had my spleen removed.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline up to 30 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline up to 30 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline up to 30 months 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

Pivotal Trial

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

No Placebo-Only Group

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

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 / 14Eligibility 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 primarily aim to modulate the immune system to reduce inflammation and prevent further damage to the nervous system. Common treatments include interferon beta, which reduces inflammatory cell migration across the blood-brain barrier, and glatiramer acetate, which shifts the immune response from a pro-inflammatory to an anti-inflammatory state. Oral therapies like dimethyl fumarate and teriflunomide inhibit immune cell activation and proliferation. Bruton's Tyrosine Kinase (BTK) inhibitors, such as Remibrutinib, target B-cell and myeloid cell signaling pathways, potentially reducing the activity of these immune cells in MS. These mechanisms are crucial for MS patients as they help manage relapses, slow disease progression, and improve quality of life by minimizing neurological damage.

Therapeutic management of severe relapses in multiple sclerosis.