Remibrutinib vs Teriflunomide for Multiple Sclerosis

(REMODEL-1 Trial)

Recruiting at 240 trial locations

Overseen By Salvatore Napoli

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: Leflunomide, Methotrexate, CYP3A4 inhibitors, others

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 aims to evaluate the effectiveness of two treatments, remibrutinib and teriflunomide, for individuals with relapsing multiple sclerosis (RMS). The goal is to determine which drug better controls symptoms while ensuring safety. Individuals who have experienced at least one multiple sclerosis relapse in the past year or two may qualify for this study. Participants will be assigned to different groups to test each treatment and observe the outcomes. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to 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, and those with active immune system diseases treated with certain immune therapies may be excluded.

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

Research has shown that remibrutinib is usually well-tolerated, with most people not experiencing serious side effects, even at higher doses. Studies across various conditions have consistently found it to be safe.

Teriflunomide has received FDA approval for treating multiple sclerosis, indicating its safety for this use. However, as with any medication, some individuals might still experience side effects.

Both treatments appear safe based on past studies, but individual reactions can vary. It is important to consult a healthcare provider with any concerns. ^{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), which is a different approach from most existing multiple sclerosis (MS) treatments like interferons or glatiramer acetate that focus on modulating the immune system more broadly. This targeted action has the potential to more precisely address the underlying cause of MS with potentially fewer side effects. Researchers are excited about Remibrutinib because this specificity could lead to more effective management of MS symptoms, offering hope for improved quality of life for patients.

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

This trial will compare Remibrutinib and Teriflunomide for treating relapsing multiple sclerosis (RMS). Studies have shown that Remibrutinib, which participants in this trial may receive, can help treat RMS by reducing inflammation in the nervous system. This reduction may lower the immune system's attack on the nervous system without affecting important immune cells called B cells or T cells. Early research suggests that patients taking Remibrutinib experienced fewer relapses compared to those on other treatments. In contrast, Teriflunomide, another treatment option in this trial, is an approved medication for RMS and has been shown to slow the disease's progression. Both treatments aim to manage symptoms and prevent further damage, but Remibrutinib is being studied for its potential to offer a new way to manage RMS. ^{1 2 6 7 8}

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) 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.

Inclusion Criteria

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

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

My condition meets the 2017 criteria for RMS diagnosis.

Exclusion Criteria

Suicidal ideation or behavior

I am at risk for hepatitis reactivation.

I have had my spleen removed.

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 and teriflunomide

30 months

Extension Part

Open-label, single-arm, fixed-dose design where 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 be randomly assigned to receive either Remibrutinib or Teriflunomide while their health outcomes are monitored.

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

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]

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]

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 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]

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 (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 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]

Citations

1. 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).

2. 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)

3. 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 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37633912/

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

5. 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 ...

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

Remibrutinib (LOU064) inhibits neuroinflammation driven by B ... Remibrutinib (LOU064) inhibits neuroinflammation driven by B cells and myeloid cells in preclinical models of multiple sclerosis · Abstract.

8. 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.