Multiple Sclerosis > Remibrutinib

Remibrutinib vs Teriflunomide for Multiple Sclerosis

(REMODEL-2 Trial)

Recruiting in Palo Alto (17 mi)

+283 other locations

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Novartis Pharmaceuticals

Must not be taking: Leflunomide, Methotrexate, CYP3A4 inhibitors

Disqualifiers: PPMS, CNS disease, substance abuse, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that participants should not use strong CYP3A4 inhibitors or inducers within two weeks before starting the trial, so you may need to avoid certain medications.

What data supports the effectiveness of the drug teriflunomide for multiple sclerosis?

Teriflunomide is an oral drug that has been shown to be effective in treating relapsing forms of multiple sclerosis (MS) by reducing relapses and disease activity, as demonstrated in clinical trials and real-world studies. It is generally well tolerated and has been approved for use in both adults and children aged 10 years and older.

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Is teriflunomide generally safe for humans?

Teriflunomide (Aubagio) is generally well tolerated in patients with relapsing multiple sclerosis, with no new safety concerns identified during long-term treatment of 10 years or more.

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How does the drug Remibrutinib differ from Teriflunomide in treating multiple sclerosis?

Remibrutinib is a novel treatment being compared to Teriflunomide, which is an established oral drug for relapsing multiple sclerosis that works by inhibiting an enzyme to reduce immune cell activity. Teriflunomide is known for its once-daily oral administration and has been shown to be effective in reducing relapses and disease activity in multiple sclerosis.

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Eligibility Criteria

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.

Inclusion Criteria

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

My neurological condition has been stable for the last month.

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

Exclusion Criteria

Suicidal ideation or behavior

My condition has lasted over 10 years and I have minimal disability.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Core Part

Randomized, double-blind, double-dummy, active comparator-controlled, fixed-dose, parallel-group study comparing remibrutinib versus teriflunomide

30 months

Extension Part

Open-label, single-arm, fixed-dose design where eligible participants are treated with remibrutinib

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Participant Groups

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.

Group I: Remibrutinib - Extension (on teriflunomide in Core) Experimental Treatment 1 Intervention

Participants on teriflunomide in Core will switch to remibrutinib tablet

Group II: Remibrutinib - Extension Experimental Treatment 1 Intervention

Participants on remibrutinib in Core will continue on remibrutinib tablet

Group III: Remibrutinib - Core Experimental Treatment 1 Intervention

Remibrutinib tablet and matching placebo of teriflunomide capsule

Group IV: Teriflunomide - Core Active Control 1 Intervention

Teriflunomide capsule and matching placebo remibrutinib tablet

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Neurology Associates, PA Maitland, FL

Novartis Investigative Site Greer, SC

Georgetown University Hospital Research Washington, United States

University of Washington MS Clinic Seattle, WA

More Trial Locations

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Real-life outcomes of teriflunomide treatment in patients with relapsing multiple sclerosis: TAURUS-MS observational study. [2022] Teriflunomide is a once-daily oral immunomodulatory agent approved for the treatment of relapsing-remitting multiple sclerosis (MS). We aimed to obtain data on the effectiveness, tolerability, and subject satisfaction with teriflunomide (Aubagio®) under clinical practice conditions in unselected MS patients.

2. Switzerland pubmed.ncbi.nlm.nih.gov

Teriflunomide: Pediatric First Approval. [2021] Teriflunomide (Aubagio®), which was developed by Sanofi, is an oral immunomodulatory agent targeting the mitochondrial enzyme dihydroorotate dehydrogenase and available to adults to treat relapsing-remitting multiple sclerosis (MS). On 18 June 2021, teriflunomide received its first approval in this indication in pediatric patients aged ≥ 10 years in the EU. This article summarizes the milestones in the development of teriflunomide leading to this first pediatric approval for relapsing-remitting MS.

3. United States pubmed.ncbi.nlm.nih.gov

Teriflunomide (Aubagio®) for the treatment of multiple sclerosis. [2021] Teriflunomide (Aubagio®) is a once-daily oral immunomodulatory disease modifying therapy (DMT) presently approved in several regions, including Europe, North America, Latin America and Australia, for the treatment of relapsing forms of multiple sclerosis (RMS; RRMS). The therapeutic mode of action of teriflunomide in MS continues to be investigated. This review summarizes the main efficacy and safety results of the clinical trial program leading to teriflunomide's approval, highlights a number of practical clinical considerations, and overviews its presumed therapeutic mode of action (MOA) based on pharmacokinetic and pharmacodynamic observations and the growing body of teriflunomide-related in vitro, pre-clinical (animal model), and in vivo human studies.

4. New Zealand pubmed.ncbi.nlm.nih.gov

Teriflunomide: A Review in Relapsing-Remitting Multiple Sclerosis. [2021] Teriflunomide (Aubagio®) is a disease-modifying immunomodulatory drug with anti-inflammatory properties that selectively and reversibly inhibits the mitochondrial enzyme dihydro-orotate dehydrogenase, with consequent inhibition of de novo pyrimidine synthesis and reduced lymphocyte proliferation. Based on extensive evidence from randomized controlled trials (RCTs) and the real-world setting, oral teriflunomide is an effective and generally well tolerated treatment in patients with relapsing multiple sclerosis (MS), with these benefits maintained during long-term treatment (≥ 10 years) and no new safety signals identified. In pivotal RCTs in this patient population, teriflunomide provided significantly better efficacy than placebo (TEMSO and TOWER) and was as effective as interferon β-1a (TENERE) in terms of improvements in clinical outcomes (such as reduced annualized relapse rates, prevention of disability progression) and/or MRI-assessed disease activity measures. Albeit head-to-head trials would definitively establish the relative efficacy of oral disease-modifying therapies, given its convenient oral regimen and beneficial effects in reducing relapses and disease activity, teriflunomide remains an effective option for the management of relapsing-remitting MS (RRMS).

5. Germany pubmed.ncbi.nlm.nih.gov

Real-world outcomes of teriflunomide in relapsing-remitting multiple sclerosis: a prospective cohort study. [2022] To explore efficacy, risk factors, safety, and persistence of teriflunomide in relapsing-remitting multiple sclerosis (RRMS) cohort.

6. Netherlands pubmed.ncbi.nlm.nih.gov

Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes. [2022] Teriflunomide 14 mg (Aubagio®) is a once-daily, oral drug approved for the treatment of relapsing forms of multiple sclerosis (MS). While the efficacy and safety of teriflunomide have been thoroughly characterised across an extensive clinical program, we were interested in studying performance of the drug with respect to quality-of-life (QoL) outcomes in persons with MS in a real-world setting.

7. England pubmed.ncbi.nlm.nih.gov

Meta-analysis of adverse events in recent randomized clinical trials for dimethyl fumarate, glatiramer acetate and teriflunomide for the treatment of relapsing forms of multiple sclerosis. [2021] Trials of dimethyl fumarate (DMF) and teriflunomide, two new oral therapies for relapsing-remitting multiple sclerosis (RRMS) were recently published [1, 2, 3]. A comparison of their safety against glatiramer acetate-a prevalent injectable treatment-is relevant to inform therapy-switching decisions. The study objective was to conduct a systematic review and mixed treatment comparison of total AEs in RCTs of dimethyl fumarate 240 mg bid (DMF2) or tid (DMF3), glatiramer acetate 20 mg injectable daily (GA), and teriflunomide 7 mg (TERI7) or 14 mg (TERI14) daily in RRMS patients.

8. New Zealand pubmed.ncbi.nlm.nih.gov

Teriflunomide: a review of its use in relapsing multiple sclerosis. [2021] Teriflunomide (Aubagio™) is the main active metabolite of leflunomide, an established disease-modifying anti-rheumatic drug. Teriflunomide is an inhibitor of de novo pyrimidine synthesis, reducing lymphocyte proliferation, amongst other immunomodulatory effects; autoimmunity is believed to be one of the potential mechanisms of disease for multiple sclerosis. Teriflunomide is considered cytostatic but not cytotoxic: it does not affect resting or slowly dividing lymphocytes. This article reviews the available pharmacological properties of oral teriflunomide and its clinical efficacy and tolerability in patients with relapsing multiple sclerosis. While both the 7 and the 14 mg/day dosages are discussed, the 7 mg/day dosage is not approved in the EU. Both dosages are approved in the USA. In phase III trials, teriflunomide 7 or 14 mg/day was consistently demonstrated to be more effective than placebo and as effective as interferon beta-1a in the prevention of relapses in patients with relapsing forms of multiple sclerosis; moreover, teriflunomide 14 mg/day was also consistently shown to be more effective than placebo in prevention of disability progression. Teriflunomide was generally well tolerated in these patients. Long-term, extension data were generally similar to those observed in the shorter-term trials. Teriflunomide is associated with increased liver enzyme levels, and is contraindicated in pregnant patients because of a potential risk of teratogenicity. As an oral treatment, it offers an alternative to the traditional, parenteral, disease-modifying therapies; however, further investigation into the efficacy and/or tolerability differences between teriflunomide and other available oral drugs would be of great use in the placement of this drug. At present, given the relatively limited long-term data, it is difficult to draw definite conclusions with regard to safety; however, as teriflunomide is the main active metabolite of leflunomide, long-term safety data can be extrapolated from the large amount of post-approval data available regarding its parent drug. Oral teriflunomide is a valuable addition to available treatment options for patients with relapsing multiple sclerosis, in particular those patients who prefer an oral drug.