Multiple Sclerosis (MS) Primary Progressive
Conditions
Brief summary
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.
Interventions
DRUGOrelabrutinib
Orally
DRUGPlacebo
Orally
Sponsors
Zenas BioPharma (USA), LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 18 to 60 years of age, inclusive * Diagnosed with Primary Progressive MS (PPMS) according to 2017 McDonald criteria * Participant must have documented evidence of disability progression observed during the 24 months before screening. * Expanded disability status scale (EDSS) score between 3.0 to 6.5 points, inclusive, at Screening.
Exclusion criteria
* Diagnosed with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) * Immunologic disorder other than MS or any other conditions requiring oral, intravenous (IV), intramuscular, or intra-articular corticosteroid therapy. * History or current diagnosis of other neurological disorders that may mimic MS * History of any other significant active medical condition * History of suicidal behavior within 6 months prior to Screening * Any prior history of malignancy if no recurrence within 5 years * Patients on anticoagulation, or antiplatelet therapy will be excluded * Patients took strong/moderate CYP3A inhibitors or strong/moderate CYP3A inducerswithin 14 days * Clinically significant laboratory abnormalities at Screening. * Any allergy, contraindication, or inability to tolerate orelabrutinib or any of the excipients in the study intervention * Vaccination with live or live-attenuated virus vaccine within 1 month prior to Screening * History of alcohol abuse or alcohol use disorder or other drug abuse within 12 months prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to onset of composite confirmed disability progression (cCDP) , confirmed over at least 12 weeks (12-week cCDP) | Up to approximately 120 weeks | * 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to onset of composite confirmed disability progression (cCDP) , confirmed over at least 24 weeks (24-week cCDP) | Up to approximately 120 weeks | — |
| Time to onset of confirmed disability progression (CDP) , confirmed over at least 24 weeks (24-week CDP) | Up to approximately 120 weeks | 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. |
| MRI T2 lesion | Up to approximately 120 weeks | The total number of new/enlarging T2 lesions on MRI scans of the brain from baseline to Week 120 |
| 12-week CDP | Up to approximately 120 weeks | Time to onset of CDP, confirmed over at least 12 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) | 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) | Up to approximately 120 weeks | — |
| 24-week cCDI | Up to approximately 120 weeks | Time to onset of composite confirmed disability improvement (cCDI) events, confirmed over at least 24 weeks |
| 24-week CDI-9HPT | Up to approximately 120 weeks | Time to onset of CDI on 9HPT defined as ≥ 20% decrease on the 9HPT score from baseline, confirmed over at least 24 weeks |
| 24-week CDI | Up to approximately 120 weeks | Time to onset of CDI on EDSS confirmed over at least 24 weeks |
| 24-week CDI-T25FWT | Up to approximately 120 weeks | Time to onset of CDI on T25FWT defined as ≥ 20% decrease on the T25FWT score from baseline, confirmed over at least 24 weeks |
| SDMT | Up to approximately 120 weeks | The change in cognitive function as assessed by Symbol Digit Modalities Test (SDMT) |
| AEs | Up to approximately 120 weeks | 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 |
Countries
Bulgaria, Croatia, Czechia, Estonia, Georgia, Germany, Italy, Netherlands, Poland, Puerto Rico, Romania, Serbia, Slovakia, Spain, Ukraine, United States
Contacts
CONTACTPatient and Medical Information
Outcome results
None listed