Health Condition 1: G35- Multiple sclerosis
Conditions
Interventions
Intervention1: Remibrutinib: 100 mg/ matching placebo Tablet 100 mg b.i.d. oral use (blinded) for 30 months
Control Intervention1: Teriflunomide: 14 mg/ matching placebo Capsule 14 mg q.d. oral use (b
Sponsors
Novartis Healthcare Pvt Ltd
Eligibility
Inclusion criteria
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
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 Hematology parameters at screening: 1-Hemoglobin: 2-Platelets: 3-Absolute lymphocyte count 4-White blood cells: 5-Neutrophils: 6-B-cell count History or current diagnosis of significant ECG abnormalities Resting QTcF >=450 msec (male) or >=460 msec (female) at pre-treatment (prior to randomization) 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
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). Symptoms will be reported by participants at at a scheduled visit or at any other time and confirmation of relapses will be assessed by EDSS Rater | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secondary objectives (Core Part): To assess whether remibrutinib is superior to teriflunomide in 1.Delaying disability progression based on the pooled data from both identical pivotal studiesTimepoint: 1. Time to 3-month confirmed disability progression (3mCDP) on Expanded Disability Status Scale (EDSS) 2. Time to 6-month confirmed disability progression (6mCDP) on EDSS ;1. 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: 1. 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 data) Change from baseli | — |
Countries
Australia, Brazil, Canada, China, Denmark, Germany, India, Malaysia, Poland, Russian Federation, Slovakia, South Africa, Switzerland, Taiwan, Thailand, United Kingdom, United States of America, Viet Nam
Contacts
Public ContactMurugananthan K
Novartis Healthcare Pvt Ltd
Outcome results
None listed