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

The study CLOU064C12301 consists of an initial Core Part (CP) (maximum duration per participant of up to 30 months), followed by an Extension Part (EP, of up to 5 years duration) for eligible participants.

The Core Part is a randomized, double-blind, double-dummy, active comparator-controlled, fixed-dose, parallel-group, multi-center study in approximately 800 participants with relapsing multiple sclerosis (RMS).

The Extension Part is an open-label, single-arm, fixed-dose design in which eligible participants are treated with remibrutinib for up to 5 years.

A second study of identical design (CLOU064C12302) will be conducted simultaneously. Both studies will be conducted globally and data from the two studies will be pooled for some of the endpoints.

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

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

In order to maintain blinding, a double-dummy design will be used