A study to evaluate the efficacy and safety of fenebrutinib on disability progression in adult participants with Primary Progressive Multiple Sclerosis (PPMS). All eligible participants will be randomized 1:1 to either daily oral fenebrutinib (and placebo) or intravenous (IV) ocrelizumab (and placebo) in a blinded fashion through an interactive voice or web-based response system (IxRS). 985 participants were enrolled and recruited globally. Participants who discontinue study medication early or discontinue from the study will not be replaced. The Open-Label Extension (OLE) phase is contingent on a positive benefit-risk result in the Primary Analysis of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
985
Participants will receive fenebrutinib.
Participants will receive ocrelizumab.
Participants will receive ocrelizumab-matching placebo.
Participants will receive fenebrutinib-matching placebo
Alabama Neurology Associates
Homewood, Alabama, United States
Sutter East Bay Medical Foundation
Berkeley, California, United States
Fullerton Neurology and Headache Center
Fullerton, California, United States
Palo Alto Medical Foundation Research Center
Sunnyvale, California, United States
University of Colorado Denver
Aurora, Colorado, United States
Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12)
Time frame: Minimum of 120 weeks
Time to Onset of Composite 24-week CDP (cCDP24)
Time frame: Minimum of 120 weeks
Time to Onset of 12-week CDP (CDP12)
Time frame: Minimum of 120 weeks
Time to Onset of 24-week CDP (CDP24)
Time frame: Minimum of 120 weeks
Percentage Change in Total Brain Volume Assessed by Magnetic Resonance Imaging (MRI)
Time frame: From Week 24 to Week 120
Change from Baseline in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) Measured by the Multiple Sclerosis Impact Scale, 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, 96, 108 and 120
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, 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 120 weeks
Percentage of Participants with Adverse Events (AEs)
Time frame: Up to 4.7 years
Plasma Concentrations of Fenebrutinib at Specified Timepoints
Time frame: Up to 4.7 years
Percent Change from Screening in Blood Neurofilament Light Chain (NfL) Levels
Time frame: Up to Week 120
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Yale University School Of Medicine
Fairfield, Connecticut, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
Neurology Associates PA
Maitland, Florida, United States
Neurological Services of Orlando
Orlando, Florida, United States
University of South Florida
Tampa, Florida, United States
...and 179 more locations