Orelabrutinib is a CNS-penetrable BTK inhibitor. This is a phase 3, randomized, double-blind, parallel-group, multicenter study to evaluate the efficacy and safety of orelabrutinib compared with placebo in patients with PPMS. Patients will be treated for approximately 30 to 60 months, with a minimum treatment duration of 12 months. The study will enroll approximately 705 subjects in a 2:1 randomization (orelabrutinib: placebo), globally.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
705
Orally
Orally
Neurology Associates, PA
Maitland, Florida, United States
RECRUITINGPremier Neurology
Greenville, South Carolina, United States
RECRUITINGTime to onset of composite confirmed disability progression (cCDP) , confirmed over at least 12 weeks (12-week cCDP)
* Expanded disability status scale (EDSS) score increase ≥ 1.0 point from baseline when the baseline score is ≤ 5.0, or ≥ 0.5 points from baseline when the baseline score is \> 5.0, OR * ≥ 20% increase in the Timed 25-Foot Walk Test (T25FWT), OR * ≥ 20% increase in the 9-hole Peg Test (9HPT)
Time frame: Up to approximately 120 weeks
Time to onset of composite confirmed disability progression (cCDP) , confirmed over at least 24 weeks (24-week cCDP)
Time frame: Up to approximately 120 weeks
Time to onset of confirmed disability progression (CDP) , confirmed over at least 24 weeks (24-week CDP)
Expanded disability status scale (EDSS) score increase ≥ 1.0 point from baseline when the baseline score is ≤ 5.0, or ≥ 0.5 points from baseline when the baseline score is \> 5.0.
Time frame: Up to approximately 120 weeks
MRI T2 lesion
The total number of new/enlarging T2 lesions on MRI scans of the brain from baseline to Week 120
Time frame: Up to approximately 120 weeks
12-week CDP
Time to onset of CDP, confirmed over at least 12 weeks
Time frame: Up to approximately 120 weeks
Time to onset of CDP defined as ≥ 20% increase on 9-hole Peg Test (9HPT) from baseline, confirmed over at least 12 weeks (12-week CDP-9HPT)
Time frame: Up to approximately 120 weeks
Time to onset of CDP defined as ≥ 20% increase on Timed 25-Foot Walk Test (T25FWT) from baseline, confirmed over at least 12 weeks (12-week CDP-T25FWT)
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Time frame: Up to approximately 120 weeks
24-week cCDI
Time to onset of composite confirmed disability improvement (cCDI) events, confirmed over at least 24 weeks
Time frame: Up to approximately 120 weeks
24-week CDI-9HPT
Time to onset of CDI on 9HPT defined as ≥ 20% decrease on the 9HPT score from baseline, confirmed over at least 24 weeks
Time frame: Up to approximately 120 weeks
24-week CDI
Time to onset of CDI on EDSS confirmed over at least 24 weeks
Time frame: Up to approximately 120 weeks
24-week CDI-T25FWT
Time to onset of CDI on T25FWT defined as ≥ 20% decrease on the T25FWT score from baseline, confirmed over at least 24 weeks
Time frame: Up to approximately 120 weeks
SDMT
The change in cognitive function as assessed by Symbol Digit Modalities Test (SDMT)
Time frame: Up to approximately 120 weeks
AEs
Safety as assessed by the nature, severity, and incidence of adverse events (AEs) (graded according to National Cancer Institute-Common Terminology Criteria for AEs, NCI-CTCAE version 5.0); vital signs; electrocardiograms (ECGs); and clinical laboratory safety parameter
Time frame: Up to approximately 120 weeks