Remibrutinib vs Teriflunomide for Multiple Sclerosis

(REMODEL-2 Trial)

Recruiting at285 trial 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. ^{1 2 3 4 5}

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. ^{1 2 3 4 6}

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. ^{1 3 4 7 8}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

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

Treatment Details

Interventions

• Remibrutinib (Bruton's Tyrosine Kinase (BTK) Inhibitor)
• Teriflunomide (Immunomodulator)

Trial Overview 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.

Participant Groups

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

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

In a study of 1128 patients with relapsing-remitting multiple sclerosis, teriflunomide significantly reduced the annualized relapse rate from 0.87 to 0.35 over 24 months, indicating its effectiveness in managing the disease.

Patient satisfaction with teriflunomide was high, with significant improvements in effectiveness, convenience, and overall satisfaction reported after 24 months, while the safety profile was consistent with previous clinical trials, with 35.8% experiencing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-life outcomes of teriflunomide treatment in patients with relapsing multiple sclerosis: TAURUS-MS observational study. Kallmann, BA., Tiel-Wilck, K., Kullmann, JS., et al.[2022]

Teriflunomide (Aubagio®) is an oral medication that works by targeting the mitochondrial enzyme dihydroorotate dehydrogenase, helping to modulate the immune response in patients with relapsing-remitting multiple sclerosis (MS).

On June 18, 2021, teriflunomide was approved for use in pediatric patients aged 10 years and older in the EU, marking a significant milestone in its development for treating MS in younger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriflunomide: Pediatric First Approval. Paik, J.[2021]

Teriflunomide (Aubagio®) is an effective once-daily oral treatment for relapsing forms of multiple sclerosis (RMS), approved in multiple regions including Europe and North America.

The review discusses teriflunomide's safety and efficacy based on extensive clinical trials, while also exploring its therapeutic mechanism of action, which is still being researched through various studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriflunomide (Aubagio®) for the treatment of multiple sclerosis. Bar-Or, A.[2021]

In a study of 217 patients with relapsing-remitting multiple sclerosis (RRMS) treated with teriflunomide, 79% achieved no evidence of disease activity (NEDA) after 12 months, indicating its efficacy in managing the condition.

The most common side effects included hair thinning and liver enzyme elevation, which led to some patients discontinuing treatment, particularly within the first three months. Persistence rates for teriflunomide were 86.9% at 6 months, 72.4% at 12 months, and 52.8% at 24 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world outcomes of teriflunomide in relapsing-remitting multiple sclerosis: a prospective cohort study. Zhang, Y., Yin, H., Zhang, D., et al.[2022]

In a real-world study involving 200 patients with relapsing multiple sclerosis, teriflunomide demonstrated stable quality of life over 24 months, with significant reductions in relapse activity compared to the pre-baseline period.

The study indicated high treatment adherence and acceptability of teriflunomide, as reflected in patient-reported outcomes, with no substantial changes in fatigue and a marginal increase in reported disability.

NCBI (Pubmed)

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. Hestvik, ALK., Frederiksen, JL., Nielsen, HH., et al.[2022]

Teriflunomide is an effective oral treatment for relapsing multiple sclerosis, showing better efficacy than placebo and comparable effectiveness to interferon beta-1a in preventing relapses and disability progression, based on phase III trials.

While generally well tolerated, teriflunomide can increase liver enzyme levels and is contraindicated in pregnancy due to potential teratogenic risks, highlighting the need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriflunomide: a review of its use in relapsing multiple sclerosis. Garnock-Jones, KP.[2021]

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]

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

Teriflunomide: Pediatric First Approval. [2021]

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

Teriflunomide (Aubagio®) for the treatment of multiple sclerosis. [2021]

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

Teriflunomide: A Review in Relapsing-Remitting Multiple Sclerosis. [2021]

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

Real-world outcomes of teriflunomide in relapsing-remitting multiple sclerosis: a prospective cohort study. [2022]

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]

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]

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

Teriflunomide: a review of its use in relapsing multiple sclerosis. [2021]