A study to evaluate the efficacy and safety of fenebrutinib on disability progression and relapse rate in adult participants with RMS. Eligible participants will be randomized 1:1 to either fenebrutinib or teriflunomide. At the end of the DBT phase (after disclosure of the DBT results), the Sponsor will determine whether or not to initiate the open-label extension phase of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
746
Participants will receive fenebrutinib.
Participants will receive teriflunomide.
Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo.
Annualized Relapse Rate (ARR)
Time frame: Minimum of 96 weeks
Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12)
Time frame: Minimum of 96 weeks
Time to Onset of Composite 24-week Confirmed Disability Progression (cCDP24)
Time frame: Minimum of 96 weeks
Time to Onset of 12-week Confirmed Disability Progression (CDP12)
Time frame: Minimum of 96 weeks
Time to Onset of 24-week Confirmed Disability Progression (CDP24)
Time frame: Minimum of 96 weeks
Total Number of T1 Gadolinium Enhancing (Gd+) Lesions, New and/or Enlarging T2-weighted Lesions as Detected by Magnetic Resonance Imaging (MRI)
Time frame: Baseline, Weeks 12, 24, 48 and 96
Percentage Change in Total Brain Volume from Week 24 as Assessed by MRI
Time frame: From Week 24 to Week 96
Change in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) Measured by the Multiple Sclerosis, 29-Item [MSIS-29] Physical Scale
The MSIS-29, Version 2 is a 29-item patient-reported measure of the physical and psychological impacts of MS. Participants are asked to rate how much their functioning and well-being has been impacted over the past 14 days on a 4-point scale, from "Not at all" (1) to "Extremely" (4). The physical score is the sum of items 1-20, which is then transformed to a 0-100 scale. The psychological score is the sum of items 21-29, transformed to a 0-100 scale. Higher scores indicate a greater impact of MS.
Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96
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University of Alabama Birmingham
Birmingham, Alabama, United States
Alabama Neurology Associates
Homewood, Alabama, United States
Center for Neurology and Spine - Phoenix - Hunt - PPDS
Phoenix, Arizona, United States
Profound Research, LLC
Carlsbad, California, United States
University of California Irvine
Irvine, California, United States
SC3 Research Group, Inc
Pasadena, California, United States
University of Colorado Denver
Aurora, Colorado, United States
Mountain View Clinical Research
Denver, Colorado, United States
Advanced Neurology of Colorado, LLC
Fort Collins, Colorado, United States
Neurology Associates, PA; Research Department
Maitland, Florida, United States
...and 150 more locations
Time to Onset of 12-week Confirmed 4-point worsening in Symbol Digit Modality Test (SDMT) Score
The SDMT is used for detecting the presence of cognitive impairment and changes in cognitive functioning over time and in response to treatment. The SDMT is brief, is easy to administer test, and involves a simple substitution task. Using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses will be collected only orally, and administration time is approximately 5 minutes. The number of correct responses in 90 seconds will be considered the SDMT score. A decrease by 4 points on the SDMT score from baseline represents a clinically meaningful change in cognitive processing. The SDMT score ranges from 0 to 110. The higher the results, the better processing speed/working memory.
Time frame: Minimum of 96 weeks
Change from Baseline to Week 48 in the Concentration of Blood Neurofilament Light Chain (NfL)
Time frame: Up to 48 weeks
Percentage of Participants with Adverse Events (AEs)
Time frame: Up to 4.5 years
Plasma Concentrations of Fenebrutinib at Specified Timepoints
Time frame: Up to 4.5 years
Time to Onset of Composite 12-week Confirmed Progression Independent of Relapse Activity (cPIRA12)
Time frame: Minimum of 96 weeks