Health Condition 1: G00-G99- Diseases of the nervous system
Conditions
Sponsors
Merck Healthcare KGaA
IQVIA RDS India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: Age 1. Are 18 to 55 years of age at the time of signing the informed consent. Type of Participant and Disease Characteristics 2. Are diagnosed with RMS (RRMS or SPMS with relapses) in accordance with 2017 Revised McDonald criteria (Thompson 2018). 3. 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 T1 Gd plus lesion within 6 months prior to randomization. 4. Have an EDSS score of 0 to 5.5 at Screening and Baseline (Day 1) a. Participants with an EDSS score less than or equal to 2 at Screening and Baseline (Day 1) are only eligible for participation if their disease duration (time since onset of symptoms) is no more than 10 years. 5. Are neurologically stable for = 30 days prior to both Screening and Baseline (i.e., no new signs or symptoms referable to the CNS for = 30 days). Sex 6. Are female or male a. Male Participants Agree to the following during the study intervention period and for at least 2 years after study intervention due to the long elimination period for teriflunomide of 2 years, unless the participant undergoes an AEP (see Appendix 8) with a confirmed teriflunomide level of less than 0.02 mg per L after the last dose of study intervention: • Refrain from donating sperm PLUS, either: • Abstain from intercourse with a woman of childbearing potential. OR • Use a male condom: o When having sexual intercourse with a woman of childbearing potential, who is not currently pregnant, and advise her to use a highly effective contraceptive method with a failure rate of b. Female participants • Are not pregnant or breastfeeding, and at least one of the following conditions applies: o Not a woman of childbearing potential. OR o If a woman of childbearing potential, use a highly effective contraceptive method (i.e., with a failure rate of less than 1 percent per year), preferably with low user dependency, as described in Appendix 3 for the following time periods: • Before the first dose of the study intervention(s), if using hormonal contraception: • Has completed at least one 4-week cycle of an oral contraception pill and either had or has begun her menses OR • Has used a depot contraceptive or extended-cycle oral contraceptive for at least 28 days and has a documented negative pregnancy test using a highly sensitive assay. AND o A barrier method, as described in Appendix 3 • Have a negative serum or highly sensitive urine pregnancy test, as required by local regulations, within 4 to 8 weeks and a highly sensitive urine pregnancy test at Baseline before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. • During the Intervention Period For at least 2 years after study intervention due to the long elimination period for teriflunomide of (up to) 2 years, unless the participant undergoes an AEP (see Appendix 8) with a confirmed teriflunomide level of less than 0.02 mg/L after the last dose of study intervention and agree not to donate eggs (ova, oocytes) for reproduction during this period (see Append
Exclusion criteria
Exclusion criteria: Medical Conditions 1. Participants diagnosed with progressive MS, in accordance with the 2017 Revised McDonald criteria, as follows o Participants with primary progressive MS. o Participants with SPMS without evidence of relapse. 2. Disease duration more than 10 years in participants with an EDSS less than or equal to 2.0 at Screening and Baseline (Day 1). 3. Immunologic disorder other than MS or any other condition requiring oral, IV, intramuscular, or intra-articular corticosteroid therapy, with the exception of well-controlled Type 2 diabetes mellitus or well-controlled thyroid disease. 4. History or current diagnosis of other neurological disorders that may mimic MS, including but not limited to neuromyelitis optica, transverse myelitis, bilateral optic neuritis of simultaneous onset, Lyme disease, HTLV-1-associated myelopathy, untreated vitamin B12 deficiency, neurosarcoidosis, cerebrovascular disorders, documented peripheral neuropathy (including polyneuropathy or mononeuropathy). 5. History or current diagnosis of PML. If a brain MRI has findings suggestive of PML, CSF JCV PCR should be performed to rule out PML (see Appendix 7). 6. Active, clinically significant viral, bacterial, or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks before or during Screening, or completion of oral anti-infectives within 2 weeks before or during Screening, or a history of recurrent infections (i.e., 3 or more of the same type of infection in a 12-month rolling period). Vaginal candidiasis, onychomycosis, and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled would not be exclusionary. 7. The participant: • Has a history of or current diagnosis of active TB OR • Is currently undergoing treatment for LTBI OR • Has an untreated LTBI as determined by documented results within 3 months of the Screening Visit of a positive TB skin test with PPD with induration more than or equal to 5 mm. OR • Has current household contacts with active TB, unless prophylaxis treatment has been completed and documented evidence that household contacts have completed treatment. OR • Has a positive QuantiFERON-TB test at Screening, unless the participant has completed chemoprophylaxis for LTBI (as per applicable local guidelines) prior to the Screening Visit. Study participants in high TB burden settings (more than 100 cases / 100,000 individuals [WHO, 2020], based on WHO TB database [WHO TB Burden Estimates]) must repeat TB testing at least annually at the visits indicated (see Schedule of Activities Section 1.3), using the assay that was negative at Screening or a replacement (see Laboratory Manual) (see Exclusion Criterion 8). In addition, participants can be tested for TB at any time during the study, at the discretion of the Investigator. Participants with documented completed appropriate LTBI treatment would not be excluded and are not required to be tested. 8. Individuals with indeterminate or positive QuantiFERON test results felt to represent a false positive result by the Investigator, with no clinical features consistent with active TB, may be evaluated with T-SPOT.TB at the request of the Investigator. In this case, if the T-SPOT.TB is negative, the individual may be enr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate superior efficacy with evobrutinib compared to teriflunomide in terms of ARRTimepoint: ARR based on qualified relapses up to 156 weeks in participants with RMS | — |
Secondary
| Measure | Time frame |
|---|---|
| To characterize the safety & tolerability of evobrutinib.Timepoint: • Safety as assessed by the nature, severity, & occurrence of adverse events (AEs) & adverse events of special interest (AESIs); vital signs; electrocardiograms (ECGs); absolute concentrations & CFB in immunoglobulin (Ig) levels; & clinical laboratory safety parameters up to the end of the safety follow-up period;To demonstrate the efficacy of evobrutinib relative to that of teriflunomide on disability improvementTimepoint: Time to first occurrence of 24-week CDI as measured by the EDSS up to 156 weeks;To demonstrate the efficacy of evobrutinib relative to that of teriflunomide on disability progressionTimepoint: • Time to first occurrence of 12-week confirmed disability progression (CDP) as measured by the Expanded Disability Status Scale (EDSS) up to 156 weeks • Time to first occurrence of 24-week CDP as measured by the EDSS up to 156 weeks;To demonstrate the efficacy of evobrutinib relative to that of teriflunomide on MRI lesion parametersTimepoint: • Total number of T1 Gd plus lesions based on all available MRI scans • Number of new or enlarging T2 lesions on the last available MRI scan relative to the baseline MRI scan;To demonstrate the efficacy of evobrutinib relative to that of teriflunomide on NfL concentration in serumTimepoint: NfL concentration at 12 weeks;To demonstrate the efficacy of evobrutinib relative to that of teriflunomide on patient reported symptoms & functional statusTimepoint: • Change from Baseline (CFB) in Patient Reported Outcomes Measurement Information System (PROMIS) physical function (PF) score over 96 weeks • CFB in PROMIS Fatigue score over 96 weeks | — |
Countries
Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Germany, Hong Kong, Hungary, India, Israel, Italy, Mexico, Netherlands, Peru, Poland, Portugal, Republic of Korea, Russian Federation, Serbia, Spain, Taiwan, Ukraine, United Kingdom, United States of America
Contacts
Public ContactDr. Jinu Jose
IQVIA RDS (India) Private Limited
Outcome results
None listed