Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants with Relapsing Multiple Sclerosis (RMS)

The purpose of the study is to provide efficacy, safety, and tolerability data for the investigational drug Remibrutinib as a treatment for relapsing multiple sclerosis (RMS) as compared to the approved/commercially available drug Teriflunomide. The clinical trial will be composed of 2 groups in which eligible participants will be randomized in a 1:1 ratio:

1. Remibrutinib 100 mg with Placebo Teriflunomide
2. Teriflunomide 14 mg with Placebo Reminbrutinib

In order to participate you must meet the following criteria:

• Are 18 to 55 years of age.
• Have a diagnosis of RMS according to the 2017 McDonald diagnostic criteria.
• Have 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.
• Have an EDSS score of 0 to 5.5 (inclusive).
• Have been neurologically stable within 1 month.

You will be excluded from the study if any of the following criteria apply to you:

• Have a diagnosis of primary progressive multiple sclerosis (PPMS).
• Have a disease duration of more than 10 years in participants with EDSS score of 2 or less at screening.
• Have a history of clinically significant CNS disease other than MS.
• Have ongoing substance abuse (drug or alcohol).
• Have a history of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer).
• Have a history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or Neurological symptoms consistent with PML
• Have suicidal ideation or behavior.
• Have 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.
• Have had a splenectomy.
• Have active clinically significant systemic bacterial, viral, parasitic or fungal infections.
• Have positive results for syphilis or tuberculosis testing.
• Have uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids.
• Have 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.
• Have a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody.
• Have a 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.
• Have a history of severe renal disease or creatinine level.
• Are at risk of developing or having reactivation of hepatitis.
• Have the following 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)
• Have a history or current diagnosis of significant ECG abnormalities.
• Have resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment as per central ECG reading at screening visit.
• Are using other investigational drugs.
• Have a requirement for anticoagulant medication or use of dual anti-platelet therapy.
• Have significant bleeding risk or coagulation disorders.
• Have a history of gastrointestinal bleeding.
• Have had major surgery within 8 weeks prior to screening.
• History of hypersensitivity to any of the study drugs or excipients.
• Are pregnant or nursing (lactating) female participants, prior to randomization.
• Are a woman of childbearing potential not using highly effective contraception.
• Are a sexually active male 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.
• Are using strong CYP3A4 inhibitors or 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).

This is a partial list of eligibility requirements. To inquire about your eligibility, please call the contact number provided. If you wish to inquire via email, please include the title of the study in your message.