Health Condition 1: G35- Multiple sclerosis
Conditions
Sponsors
Merck Healthcare KGaA
IQVIA RDSIndia Pvt Ltd
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 (relapsing-remitting multiple sclerosis [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 Gd+ T1 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 = 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. 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 accelerated elimination procedure with a confirmed teriflunomide level of - Refrain from donating sperm PLUS, either: - Abstain from intercourse with a Woman of Childbearing Potential (WOCBP). OR - Use a male condom: When having sexual intercourse with a WOCBP, 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: - Not a WOCBP. OR - If a WOCBP, use a highly effective contraceptive method (i.e., with a failure rate of 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 - A barrier method, - 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 accelerated elimination procedure with a confirmed teriflunomide level of after the last dose of study intervention and agree not to donate eggs (ova, oocytes) for reproduction during this period . The Investigator evaluates the effectiveness of the contraceptive method in relationship to the first dose of study intervention. -Additional req
Exclusion criteria
Exclusion criteria: 1. Participants diagnosed with progressive MS, in accordance with the 2017 Revised McDonald criteria.2. Disease duration > 10 years in participants with an EDSS = 2.0 at Screening and Baseline (Day 1).3. 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.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, cerebrospinal fluid JC virus polymerase chain reaction (CSF JCV PCR) should be performed to rule out PML.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 of 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 tuberculosis (TB)OR Is currently undergoing treatment for latent TB infection (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 purified protein derivative (PPD) with induration = 5 mm.ORHas current household contacts with active TB, unless prophylaxis treatment hasbeen completed and documented evidence that household contacts have completed treatment.OR Has a positive QuantiFERON-TB test at Screening, unless the participant hascompleted chemoprophylaxis for LTBI (as per applicable local guidelines) prior to the Screening Visit.8. If the QuantiFERON-TB test results are indeterminate, then the individuals will be evaluated with T-SPOT.TB at the request of the Investigator. In this case, if theT-SPOT.TB is negative, the individual may be enrolled (see Section 8 for exceptions to tests analyzed by a central laboratory). If T-SPOT.TB is not available, the individual is excluded from participation in the study. 9. Individuals with a diagnosis of hemochromatosis, Wilson’s disease, alpha-1-antitrypsin deficiency, or any other chronic liver disease including Gilbert’s disease will be excluded from the study.10. Individuals with elevated transferrin saturation ( > 50% transferrin saturation in males; and > 40% transferrin saturation in females) and/or with elevated ferritin levels > 500 µg/L will be excluded.11. Individuals with sickle cell anemia, thalassemia and/or any chronic blood disorder requiring blood transfusions will be excluded from the study.12. History of splenectomy at any time, or any major surgery within 2 months prior to Screening. 13. History of myocardialinfarction or cerebrovascular event within 6 months prior to Screening, or current active angina pectoris, histor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate superior efficacy with evobrutinib compared to teriflunomide in terms of Annualized Relapse Rate (ARR)Timepoint: ARR based on qualified relapses at Week 96 in participants with RMS | — |
Secondary
| Measure | Time frame |
|---|---|
| To characterize the safety and tolerability of evobrutinibTimepoint: up to Week 108;To demonstrate the efficacy of evobrutinib relative to that of teriflunomide on disability progressionTimepoint: 12-week confirmed disability progression (CDP) as measured by the Expanded Disability Status Scale (EDSS) over 96 weeks. Time to first occurrence of 24-week CDP as measured by the EDSS over 96 weeks;To demonstrate the efficacy of evobrutinib relative to that of teriflunomide on patient reported symptoms and functional statusTimepoint: Change from Baseline (CFB) in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue score at 96 weeks;To demonstrate the efficacy of evobrutinib relative to that of teriflunomide on MRI lesion parameterTimepoint: T1 Gd lesions based on assessments at Week 24, Week 48, and Week 96.T2 lesions based on assessments at Week 24, Week 48, and Week 96 | — |
Countries
Belarus, Brazil, Bulgaria, Canada, France, Germany, Greece, India, Italy, Kuwait, Latvia, Lithuania, Malaysia, Mexico, Norway, Other, Philippines, Poland, Portugal, Republic of Moldova, Romania, Russian Federation, Saudi Arabia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Thailand, Tunisia, Turkey, United States of America
Contacts
Public ContactSuneela Thatte
IQVIA RDS India Private Limited
Outcome results
None listed