Efficacy and safety of remibrutinib compared to teriflunomide in participants with relapsing multiple sclerosis, followed by long term treatment with remibrutinib

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 800

Inclusion Criteria

1. Signed informed consent obtained prior to any assessment performed (confirm at screening visit)
2. Male or female participants 18 to 55 years of age (inclusive) at screening
3. Diagnosis of RMS according to the 2017 McDonald diagnostic criteria (this would include relapsing-remitting course (RRMS) or secondary progressive (SPMS) course with disease activity) as confirmed at screening visit.
4. At least: 1 documented relapse within the previous year, OR 2 documented relapses within the previous 2 years, prior to screening, OR 1 active Gadolinium (Gd)-enhancing lesion in the 12 months prior to screening
5. EDSS score of 0 to 5.5 (inclusive) at screening and randomization
6. Neurologically stable within 1 month prior to screening and randomization (including no MS relapse in this period)

Please see protocol for complete detailed list of inclusion criteria
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 800
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Diagnosis of primary progressive multiple sclerosis (PPMS)
2. Disease duration of more than 10 years in participants with EDSS score of 2 or less at screening
3. History of clinically significant CNS disease other than MS
4. Ongoing substance abuse (drug or alcohol)
5. History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer),
6. Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or Neurological symptoms consistent with PML
7. Suicidal ideation or behavior
8. 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
9. Participants who have had a splenectomy
10. Active clinically significant systemic bacterial, viral, parasitic or fungal infections
11. Positive results for syphilis or tuberculosis testing
12. Uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids
13. 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.
14. Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody
15. History or current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or participants with moderate or severe hepatic impairment (Child-Pugh class C) or any chronic liver or biliary disease.
16. History of severe renal disease or creatinine level
17. Participants at risk of developing or having reactivation of hepatitis
18. 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 Bcell therapies, such as rituximab, ocrelizumab or ofatumumab, prior to screening)
19. History or current diagnosis of significant ECG abnormalities
20. Resting QTcF =450 msec (male) or =460 msec (female) at pretreatment (prior to randomization)
21. Use of exclusionary medication prior to screening/randomization as defined in the protocol
22. Use of other investigational drugs
23. Requirement for anticoagulant medication or use of dual anti-platelet therapy
24. Significant bleeding risk or coagulation disorders,
25. History of gastrointestinal bleeding
26. Major surgery within 8 weeks prior to screening
27. History of hypersensitivity to any of the study drugs or excipients
28. Pregnant or nursing (lactating) female participants, prior to
randomization
29. Women of childbearing potential not using highly effective
contraception
30. Sexually active males not agreeing to use condom
31. Have received any live or live-attenuated vaccines within 6 weeks of randomization or requirement to receive these vaccinations during study
32. Use of strong CYP3A4 inhibitor

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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