Evobrutinib compared to Teriflunomide in participants with Relapsing Multiple Sclerosis

Phase 1

• Conditions: Relapsing Multiple Sclerosis; MedDRA version: 20.0Level: PTClassification code 10048393Term: Multiple sclerosis relapseSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 21.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2019-004980-36-SK
• Lead Sponsor: Merck Healthcare KGaA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-05-27
• Last Update Posted: 22 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 930

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 <= 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
- Participants are neurologically stable for >= 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 long-term 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 < 0.02 µg/mL of teriflunomide as defined in protocol) before Day 1/Baseline visit (applicable to all participants previously treated with teriflunomide, or with an unknown exposure status during the DBTP and DBE period).
- Women of childbearing potential are willing to continue to use the contraceptive methods as described in protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 930
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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, with 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified