A Randomized, Double-blind, Double-dummy, Parallel-group Study, Comparing the Efficacy and Safety of Remibrutinib Versus Teriflunomide in Participants With Relapsing Multiple Sclerosis, Followed by Extended Treatment With Open-label Remibrutinib

Plain English Summary

Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS) is a Phase 3 clinical trial sponsored by Novartis Pharmaceuticals studying Relapsing Multiple Sclerosis. Tests how well Remibrutinib works compared to Teriflunomide in reducing relapses and disability in people with relapsing multiple sclerosis. For adults aged 18-55 with relapsing multiple sclerosis, diagnosed within the last 10 years. Participation involves taking study medication daily and attending regular doctor visits for up to 30 months. Alternative treatments include other MS medications like interferons or glatiramer acetate. The trial aims to enroll 1011 participants.

Official Summary

To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis (RMS)

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if 18-55 years old, diagnosed with relapsing MS, and have had at least one relapse in the last year or two. Not eligible if you have primary progressive MS, have had MS for over 10 years, or have other serious health issues. Must be neurologically stable and have a certain level of blood cells and liver function. Cannot have had major surgery, be pregnant, or have certain infections or bleeding risks. This trial is studying Relapsing Multiple Sclerosis, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how often relapses occur, helping patients understand if the treatment is effective in preventing flare-ups. The specific primary outcome measures are: Annualized relapse rate (ARR) of confirmed relapses [Core Part] (From Baseline, up to 30 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill a gap in treating relapsing multiple sclerosis by comparing a new drug to an established one. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Relapsing Multiple Sclerosis, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape suggest a high probability of approval for a new effective MS treatment. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 1011 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you have had any recent infections or surgeries. You will take a study drug daily and have regular check-ups. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 1,011 participants

Interventions

• DRUG: Remibrutinib — tablet taken orally
• DRUG: Teriflunomide — capsule taken orally

Primary Outcomes

• Annualized relapse rate (ARR) of confirmed relapses [Core Part] (From Baseline, up to 30 months)

Secondary Outcomes

• Time to 3-month confirmed disability progression (3mCDP) on Expanded Disability Status Scale (EDSS) [Core Part] (pooled data) (Baseline up to 30 months)
• Time to 6-month confirmed disability progression (6mCDP) on EDSS [Core Part] (pooled data) (Baseline up to 30 months)
• Annualized rate of new or enlarging T2 lesion [Core Part] (Baseline up to 30 months)
• Neurofilament light chain (Nfl) [Core Part] (Baseline up to 30 months)
• Number of Gd-enhancing T1 lesions per MRI scan [Core Part] (Baseline up to 30 months)

Full Eligibility Criteria

Inclusion Criteria:

* 18 to 55 years of age
* Diagnosis of RMS according to the 2017 McDonald diagnostic criteria
* At least: 1 documented relapse within the previous year. OR 2 documented relapses within the previous 2 years, OR 1 active Gadolinium (Gd)-enhancing lesion in the 12 months.
* EDSS score of 0 to 5.5 (inclusive)
* Neurologically stable within 1 month

Exclusion Criteria:

* Diagnosis of primary progressive multiple sclerosis (PPMS)
* Disease duration of more than 10 years in participants with EDSS score of 2 or less at screening
* History of clinically significant CNS disease other than MS
* Ongoing substance abuse (drug or alcohol)
* History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer),
* Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or Neurological symptoms consistent with PML
* suicidal ideation or behavior
* Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary , renal, hepatic, endocrine, metabolic, hematological disorders or gastrointestinal disease that can interfere with interpretation of the study results or protocol adherence
* Participants who have had a splenectomy
* Active clinically significant systemic bacterial, viral, parasitic or fungal infections
* Positive results for syphilis or tuberculosis testing
* Uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids
* Active, chronic disease of the immune system (including stable disease treated with immune therapy (e.g. Leflunomide, Methotrexate)) other than MS (e.g. rheumatoid arthritis, systemic lupus erythematosus, etc.) with the exception of well-controlled diabetes or thyroid disorder.
* Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody
* History or current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis (including all Child-Pugh classes) or hepatic failure or any chronic liver or biliary disease.
* History of severe renal disease or creatinine level
* Participants at risk of developing or having reactivation of hepatitis
* 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 as per central ECG reading at screening visit
* 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

Inclusion to Extension part:

• Participants who complete the Core Part of the study on double-blind study treatment and conduct the Accelerated Elimination Procedure (AEP)

Other inclusion and exclusion criteria may apply.

Trial Locations

• Ctr for Neurology and Spine, Phoenix, Arizona, United States
• Vladimir Royter MD APMC, Hanford, California, United States
• VA Greater LA Healthcare System, Los Angeles, California, United States
• Regina Berkovich MD PhD Inc, West Hollywood, California, United States
• CU Anschutz Med Campus, Aurora, Colorado, United States
• Colorado Neurological Research PC, Denver, Colorado, United States
• New England Institute for Clinical Research, Stamford, Connecticut, United States
• Georgetown University Hospital Research, Washington D.C., District of Columbia, United States
• Georgetown University Hospital, Washington D.C., District of Columbia, United States
• Nova Clinical Research LLC, Bradenton, Florida, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Relapsing Multiple Sclerosis, Primary Progressive Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Progressive-Relapsing Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, Demyelinating Diseases

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