Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS) (REMODEL-1)

Korábbi kezelés

• Ongoing substance abuse (drug or alcohol)
• 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.
• Use of other investigational drugs
• Major surgery within 8 weeks prior to screening
• Pregnant or nursing (lactating) female participants, prior to randomization
• 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:

Más betegség

• 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
• 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
• 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
• Active clinically significant systemic bacterial, viral, parasitic or fungal infections
• Positive results for syphilis or tuberculosis testing
• 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.
• Participants at risk of developing or having reactivation of hepatitis
• History of gastrointestinal bleeding
• History of hypersensitivity to any of the study drugs or excipients

Laborértékek

• History of severe renal disease or creatinine level
• 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)
• Requirement for anticoagulant medication or use of dual anti-platelet therapy Significant bleeding risk or coagulation disorders,

Egyéb

• Diagnosis of primary progressive multiple sclerosis (PPMS)
• suicidal ideation or behavior
• Participants who have had a splenectomy
• 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
• Women of childbearing potential not using highly effective contraception
• Sexually active males not agreeing to use condom
• 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

• 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