Health Condition 1: G35- Multiple sclerosis
Conditions
Interventions
Intervention1: Remibrutinib: 100 mg/ matching placebo Tablet 100 mg b.i.d. oral use (blinded) once daily
Control Intervention1: Teriflunomide: 14 mg/ matching placebo Capsule 14 mg q.d. oral use (blin
Sponsors
Novartis Healthcare Pvt Ltd
Eligibility
Inclusion criteria
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 RRMS or active SPMS) 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 Multiple Sclerosis (MS) relapse in this period).
Exclusion criteria
Exclusion criteria: 1. Disease duration of more than 10 years in participants with EDSS score of 2 or less at screening 2. History of clinically significant Central Nervous System (CNS) disease (e.g. stroke, traumatic brain or spinal injury, history or presence of myelopathy) or neurological disorders which may mimic MS at screening 3. Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or neurological symptoms consistent with PML prior to randomization 4. Score â??yes ? on item 4 or item 5 of the suicidal ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS), if this ideation occurred in the past 6 months, or â??yes ? on any item of the suicidal behavior section, except for the â??Non-Suicidal Self-Injurious Behavior ? (item also included in the suicidal behavior section), if this behavior occurred in the past 2 years, prior to randomization 5. Participants who have had a splenectomy 6. Active clinically significant systemic bacterial, viral, parasitic or fungal infections in the judgement of the investigator prior to randomization (e.g. infections requiring hospitalization or i.v. antibiotics) 7. Active, chronic disease of the immune system (including stable disease treated with immune therapy, eg. leflunomide, methotrexate) other than MS (e.g. rheumatoid arthritis, systemic lupus erythematosus, etc.) with the exception of well-controlled diabetes or thyroid disorder. 8. Participants with a known immunodeficiency syndrome (acquired immunodeficiency syndrome (AIDS), hereditary immune deficiency, drug induced immune deficiency), or tested positive for Human immunodeficiency virus (HIV) antibody, at screening 9. Resting QT interval corrected by Fridericiaâ??s formula (QTcF) >=450 msec (male) or >=460 msec (female) at pre-treatment (prior to randomization) 10. Use of exclusionary medication prior to screening/randomization 11. Requirement for anticoagulant medication (e.g. warfarin or Novel Anti-Coagulants (NOAC)) or use of dual anti-platelet therapy (e.g. acetylsalicylic acid + clopidogrel). The use of acetylsalicylic acid up to 100 mg/day or clopidogrel is permitted 12. Significant bleeding risk or coagulation disorders, at screening 13. Have received any live or live-attenuated vaccines (including but not limited to varicella-zoster virus or measles, oral polio, nasal influenza) within 6 weeks prior to randomization or requirement to receive these vaccinations at any time during study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate that remibrutinib (100 mg b.i.d. p.o.) is superior to teriflunomide (14 mg q.d. p.o.) in reducing the frequency of confirmed relapsesTimepoint: Annualized relapse rate (ARR) of confirmed relapses (The number of confirmed relapses per year) | — |
Secondary
| Measure | Time frame |
|---|---|
| ? Key secondary objectives (Core Part): To assess whether remibrutinib is superior to teriflunomide in ? Delaying disability progression based on the pooled data from both identical pivotal studiesTimepoint: ? Time to 3-month confirmed disability progression (3mCDP) on Expanded Disability Status Scale (EDSS) ? Time to 6-month confirmed disability progression (6mCDP) on EDSS ; ? Key secondary objectives (Core Part): To assess whether remibrutinib is superior to teriflunomide in ? Reducing new inflammatory activity on MRI, based on MRI cohort dataTimepoint: ? Number of new or enlarging T2 lesions on MRI per year (annualized T2 lesion rate) ? Total number of Gd-enhancing T1 lesions per MRI scan ; ? Key secondary objectives (Core Part): To assess whether remibrutinib is superior to teriflunomide in ? Reducing neuronal damageTimepoint: ? Neurofilament light chain (NfL) concentration in serum; ? Key secondary objectives (Core Part): To assess whether remibrutinib is superior to teriflunomide in ? Disease-Activity-free status based on pooled data from both identical pivotal studies (MRI Cohort)Timepoint: ? Percentage of participants with No Evidence of Disease Activity-3 (NEDA-3), as assessed by absence of confirmed MS relapses, 6mCDP and new/enlarging T2 lesions on MRI;Other secondary objectives (Core Part): ? To assess the effects of remibrutinib relative to teriflunomide on additional clinical and MRI endpoints [pooled data from both identical pivotal studies will be used as indicated in the endpoint column]Timepoint: ?Time to first confirmed relapse ?Time to 6-month confirmed disability improvement(6mCDI)on EDSS (pooled data) ?Change from baseline in (SDMT) (pooled data) ?Time to 6-month confirmed worsening by at least 20% in the: ?(T25FW) (pooled data) ?Timed 9-hole peg test (9HPT) (pooled data) ?Time to composite 6-month confirmed disability progression,as evaluated by 6mCDP or 6-month confirmed worsening by at least 20% in T25FW or 9HPT (pooled | — |
Countries
Argentina, Belgium, Bulgaria, Chile, China, Colombia, Croatia, Czech Republic, France, Germany, Guatemala, Hong Kong, Hungary, India, Italy, Latvia, Lithuania, Malaysia, Netherlands, Poland, Russian Federation, Serbia, Slovakia, Spain, Switzerland, United Kingdom, United States of America
Contacts
Public ContactMurugananthan K
Novartis Healthcare Pvt Ltd
Outcome results
None listed