Remibrutinib vs Teriflunomide for Multiple Sclerosis

(REMODEL-2 Trial)

Recruiting at 353 trial locations

Overseen By Shahid Rafiq

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: Leflunomide, Methotrexate, CYP3A4 inhibitors

Disqualifiers: PPMS, CNS disease, substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, remibrutinib and teriflunomide, to determine which is more effective and safer for people with relapsing multiple sclerosis (RMS). RMS occurs when the immune system mistakenly attacks the protective covering of nerves, leading to symptoms like fatigue and vision problems. Individuals who have experienced at least one flare-up in the past year or two might be suitable candidates for this trial. Participants will receive either remibrutinib or teriflunomide, with some possibly switching treatments during the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for RMS.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that remibrutinib is generally safe across different doses and conditions. A detailed safety review found that most people tolerate remibrutinib well, with few experiencing serious side effects.

Regarding teriflunomide, studies have indicated it is usually safe for long-term use. In research lasting up to nine years, teriflunomide did not increase the risk of serious infections or other major health problems. Although about half of the participants reported at least one side effect, most were mild and manageable.

Both treatments have a strong safety record, making them promising options for people with relapsing multiple sclerosis. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Remibrutinib is unique because it targets Bruton's tyrosine kinase (BTK), a key player in the immune system's malfunction in multiple sclerosis (MS). Unlike standard MS treatments like interferons or glatiramer acetate, which generally modulate the immune response, remibrutinib directly hones in on BTK to potentially offer a more targeted approach in reducing inflammation and nerve damage. Researchers are excited because this mechanism could lead to fewer side effects and better outcomes for patients by specifically addressing the root cause of MS activity.

What evidence suggests that this trial's treatments could be effective for relapsing multiple sclerosis?

Research has shown that remibrutinib can reduce brain inflammation related to multiple sclerosis without directly affecting certain immune cells called B cells and T cells. This suggests it might effectively manage symptoms of relapsing multiple sclerosis (RMS). In this trial, participants will receive either remibrutinib or teriflunomide to compare their effectiveness and safety in treating RMS. Teriflunomide, already approved for RMS, has proven effective in reducing relapses and slowing the disease. The trial aims to determine which treatment better manages RMS symptoms. ^{1 2 4 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Remibrutinib
• Teriflunomide

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

In a systematic review of 3737 patients, glatiramer acetate was found to have the lowest odds of adverse events (AEs) compared to dimethyl fumarate and teriflunomide, suggesting it may be a safer option for patients with relapsing-remitting multiple sclerosis (RRMS).

Patients treated with glatiramer acetate also ranked highest in terms of quality of life (QoL) due to experiencing fewer AEs, while those on dimethyl fumarate or teriflunomide had higher odds of developing AEs.

NCBI (Pubmed)

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. Zagmutt, FJ., Carroll, CA.[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 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]

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]

Teriflunomide (Aubagio®) is an effective oral treatment for relapsing multiple sclerosis (MS), showing significant improvements in clinical outcomes and MRI measures compared to placebo and similar efficacy to interferon β-1a, based on extensive randomized controlled trials and real-world evidence.

The drug is generally well tolerated, with long-term treatment (≥ 10 years) showing sustained benefits and no new safety concerns, making it a convenient option for managing relapsing-remitting MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06846281

NCT06846281 | Efficacy and Safety of Remibrutinib After ... The purpose of this Phase 3b study is to assess the efficacy, safety and tolerability of remibrutinib after switching from ocrelizumab and compared to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10463946/

Remibrutinib (LOU064) inhibits neuroinflammation driven by B ... Remibrutinib showed efficacy in both models in absence of direct B cell depletion, broad T cell inhibition or reduction of total Ig levels.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2211034823008167

Phase 3 REMODEL I/II Trials: Efficacy, Safety, and ... The REMODEL I and II studies will investigate the efficacy, safety, and tolerability of remibrutinib versus teriflunomide to support regulatory approval ...

4. novartis.com novartis.com/clinicaltrials/study/nct05147220

Efficacy and Safety of Remibrutinib Compared to ... To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis (RMS)

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05147220

NCT05147220 | Efficacy and Safety of Remibrutinib ... Study Overview. Brief Summary. To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis (RMS).

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S221103482400693X

156. Safety of Remibrutinib across Immune-mediated ... This integrated safety analysis confirmed the consistently favorable safety profile of remibrutinib across indications and doses, including 100 mg twice daily.

7. neurology.org neurology.org/doi/10.1212/WNL.0000000000204912

Safety of Remibrutinib Across Immune-mediated Diseases ... This integrated safety analysis confirmed the consistently favorable safety profile of remibrutinib across indications and doses, including 100 mg twice daily.