Relapsing Multiple Sclerosis MedDRA version: 20.0 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Merck Healthcare KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For DBTP: - 18 years to 55 years female and male participants - Participants are diagnosed with RMS (relapsing-remitting multiple sclerosis [RRMS] or secondary progressive multiple sclerosis [SPMS] with relapses) in accordance with 2017 Revised McDonald criteria (Thompson 2018) - Participants with one or more documented relapses within the 2 years before Screening with either: a. one relapse which occurred within the last year prior to randomization, OR b. the presence of at least 1 gadolinium-enhancing (Gd+) T1 lesion within 6 months prior to randomization - Participants have Expanded Disability Status Scale (EDSS) score of 0 to 5.5 at Screening and Baseline (Day 1). Participants with an EDSS score = 30 days prior to both screening and baseline - Female participants must be neither pregnant nor breast-feeding or must lack child-bearing potential (as defined by either: post-menopausal or surgically sterile), or use an effective method of contraception for the duration of the study and at least 2 years after study intervention due to the long elimination period for teriflunomide of 2 years, unless the participant undergoes an accelerated elimination procedure - Male participants must refrain from donating sperm and/or abstain from intercourse with women of child-bearing potential or use an effective method of contraception for the duration of the study and at least 2 years after study intervention due to the long elimination period for teriflunomide of 2 years, unless the participant undergoes an accelerated elimination procedure - Participants have given written informed consent prior to any study related procedure - Other protocol defined inclusion criteria could apply. For DBE period: - Participants need to be able and willing to provide written informed consent for the DBE period before the first procedure in DBE. - Participant does not fulfill any permanent discontinuation criteria based on Week 156/EODBTP assessments. For OLE period: - participants have completed the DBE period, or are still under study treatment when enrollment into OLE is opened - but not into the longterm follow-up study -, and who, in the opinion of the Investigator, may benefit from treatment with evobrutinib. - participants are able and willing to provide written informed consent for the OLE period (e.g., before the first OLE procedure on OLE Day 1) and to comply with the study protocol. - participants have documentation of completed AEP (confirmed blood concentration level of =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: For DBTP: - Participants diagnosed with Progressive MS, in accordance with the 2017 Revised McDonald criteria as follows: a). Participants with Primary Progressive MS. b) Participants with secondary progressive MS without evidence of relapse. - Disease duration more than (>) 10 years in participants with an EDSS =< 2.0 at screening. - Immunologic disorder other than MS, or any other condition requiring oral, intravenous (IV) , intramuscular, or intra-articular corticosteroid therapy, with the exception of well-controlled Type 2 diabetes mellitus or well controlled thyroid disease. -Other protocol defined exclusion criteria could apply. For OLE period: - Participants who did not complete study intervention in DBE period. - Treatment with injectable (e.g., IV, intramuscular, intra-articular) or oral glucocorticoids, or ACTH (e.g., Acthar gel) within 30 days before OLE Day 1, with the exception of rescue treatment for MS relapse specified by the study protocol. - History of suicidal ideation or an episode of clinically severe depression (as determined by the Investigator) within 12 weeks prior to OLE Day 1. - History of abnormal laboratory results that, in the opinion of the Investigator, are indicative of a significant cardiac, endocrine, hematologic, immunologic, metabolic urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neurologic (other than MS), and/or other major diseases. Any of the following abnormal blood tests during the DBE Period requiring discontinuation of study intervention, and/or at End of DBE visit, within a week before OLE Day 1: ALT/serum glutamate pyruvate transaminase, AST/serum glutamic oxaloacetic transaminase, Total Bilirubin, amylase, or lipase, eGFR. - Female participants who have a positive pregnancy test result, are pregnant, or are currently breast feeding. - Inability to comply with study requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: For the Double-blind Treatment Period (DBTP):To demonstrate superior efficacy with evobrutinib compared to Teriflunomide in terms of Annualized Relapse Rate (ARR) For the the Double-Blind Extension (DBE) Period: To further evaluate the efficacy with evobrutinib compared to teriflunomide in terms of Annualized Relapse Rate (ARR) For the Open Label Extension (OLE) Period: To evaluate the long-term safety and tolerability of evobrutinib 45 mg twice daily (BID) in participants with Relapsing Multiple Sclerosis (RMS) over time;Secondary Objective: DBTP-to demonstrate the efficacy of evobrutinib relative to that of Teriflunomide: a.on disability progression (DP); b.on disability improvement; c.on patient reported symptoms and functional status; d.on magnetic resonance imaging (MRI) lesion parameters; e.by evaluating response on Neurofilament light chain (NfL) concentrations in serum; and f.to characterize the safety and tolerability of evobrutinib DBE Period-to further evaluate the efficacy of evobrutinib relative to that of teriflunomide: a.on DP; b.on disability improvement; c.on patient reported symptoms and functional status; d.on MRI lesion parameters; and e.to further characterize the safety and tolerability of evobrutinib. OLE Period-to evaluate the long-term efficacy of evobrutinib 45mg BID: a.in participants with RMS; b.in participants with RMS on patient reported symptoms and functional status; c.to further evaluate the longterm safety and tolerability of evobrutinib 45mg BID in participants with RMS over time.;Primary end point(s): For DBTP: ARR based on qualified relapses up to 156 weeks in participants with RMS For DBE Period: ARR based on qualified relapses in participants with RMS For OLE period: Occurrence of AEs and SAEs;Timepoint(s) of evaluation of this end point: For DBTP: up to 156 weeks For DBE Period: up to 96 weeks For OLE period: Entire OLE duration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For DBTP: a. Time to first occurrence of 12-week Confirmed Disability Progression (CDP) as measured by the Expanded Disability Status Scale (EDSS) up to 156 weeks b. Time to first occurrence of 24-week CDP as measured by the EDSS up to 156 weeks c. Time to first occurrence of 24-week Confirmed Disability Improvement (CDI) as measured by the EDSS up to 156 weeks d. Change from Baseline (CFB) in Patient Reported Outcomes Measurement Information System [PROMIS] PF score over 96 weeks e. CFB in PROMIS Fatigue score over 96 weeks f. Total number of T1 Gd+ lesions based on all available MRI scans. g. Number of new or enlarging T2 lesions on the last available MRI scan relative to the baseline MRI scan h. NfL concentration at 12 weeks i. Safety as assessed by the nature, severity, and occurrence of adverse events (AEs) and adverse events of special interest (AESIs); vital signs; electrocardiograms (ECGs); absolute concentrations and change from Baseline in immunoglobulin (Ig) levels; and clinical laboratory safety parameters up to the end of the Safety Follow-up period. For DBE Period: a. Time to first occurrence of 12-week CDP as measured by EDSS b. Time to first occurrence of 24-week CDP as measured by EDSS c. Time to first occurrence of 24-week CDP as measured by the EDSS d. CFB in PROMIS PF score over time e. CFB in PROMIS Fatigue score over time f. Total number of T1 Gd+ lesions based on all available MRI scans g. Number of new or enlarging T2 lesions on the last available MRI scan relative to the baseline MRI scan h. Safety as assessed by the nature, severity, and occurrence of AEs and AESIs; vital signs; ECGs; absolute concentrations and CFB in Ig levels; and clinical laboratory safety parameters up to the end of the Safety Follow-up period. For OLE period: a. ARR based on protocol defined qualified relapses b. Time to first occurrence of 24-week CDP as measured by EDSS c. Time to first occurrence of 24-week CDI as measured by EDSS d. SDMT ov | — |
Countries
Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Chile, Colombia, Croatia, Czechia, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Hong Kong, Hungary, India, Israel, Italy, Korea, Republic of, Mexico, Netherlands, Peru, Poland, Russian Federation, Serbia, Spain, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactCommunication Center
Merck Healthcare KGaA
Outcome results
None listed