A Study of Orelabrutinib in Patients With Secondary Progressive Multiple Sclerosis

NCT07299019
clinicaltrials.gov
Phase
Phase 3
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Recruitment status
Recruiting
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Participants
990
clinicaltrials.gov
Lead sponsor
Zenas BioPharma (USA), LLC
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Start date
2026-03-23
clinicaltrials.gov
Number of sites
69
clinicaltrials.gov

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 non-active Secondary Progress MS. Patients will be treated for approximately 24 to 60 months, with a minimum treatment duration of 12 months. The study will enroll approximately 990 subjects in a 2:1 randomization (orelabrutinib: placebo), globally.
clinicaltrials.gov
Short title
A Study of Orelabrutinib in Patients With Secondary Progressive Multiple Sclerosis
clinicaltrials.gov
Official title
A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing Orelabrutinib to Placebo in Patients With Non-active Secondary Progressive Multiple Sclerosis
clinicaltrials.gov

Control arm
Placebo
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Registry reports results
No
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Listing at source
Listed
clinicaltrials.gov
Recruitment status
Recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2030-07-01
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First posted
2025-12-23
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Registry last updated
2026-10-27
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Primary completion date
2030-06-01
clinicaltrials.gov
Start date
2026-03-23
clinicaltrials.gov

Participants
990
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Participant count basis
Estimated
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Planned participants
990
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Protocol amendments
1
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Randomisation ratio
2:1
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Number of sites
69
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Zenas BioPharma (USA), LLC
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Source registry
ClinicalTrials.gov
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Registry ID
NCT07299019
clinicaltrials.gov
ClinicalTrials.gov ID
NCT07299019
clinicaltrials.gov
Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Time to onset of confirmed disability progression (CDP) events, confirmed over at least 24 weeks

    Timeframe: 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

  1. 12 Week CDP

    Timeframe: Up to approximately 120 weeks

    Time to onset of CDP events on EDSS, confirmed over at least 12 weeks

  2. T2 lesions on MRI

    Timeframe: Up to approximately 120 weeks

    The total number of new or enlarging T2 lesions on MRI scans of the brain

  3. 24-week CDP-9-hole Peg Test

    Timeframe: Up to approximately 120 weeks

    Time to onset of CDP events on 9-hole Peg Test (9HPT), defined as ≥ 20% increase on 9HPT from baseline, confirmed over at least 24 weeks

  4. 24-week CDP-T25FWT

    Timeframe: Up to approximately 120 weeks

    Time to onset of CDP events on Timed 25-Foot Walk Test (T25FWT), defined as ≥ 20% increase on T25FWT from baseline, confirmed over at least 24 weeks

  5. 24-week CDI

    Timeframe: Up to approximately 120 weeks

    Time to onset of confirmed disability improvement (CDI) events on EDSS, defined as ≥ 1.0-point decrease on the EDSS score from baseline when the baseline score is ≤ 5.0, or ≥ 0.5 points from baseline when the baseline score is \> 5.0, confirmed over at least 24 weeks

  6. 24-week CDI-9HPT

    Timeframe: Up to approximately 120 weeks

    Time to onset of CDI events on 9HPT, defined as ≥ 20% decrease on the 9HPT score from baseline, confirmed over at least 24 weeks

  7. 24-week CDI-T25FWT

    Timeframe: Up to approximately 120 weeks

    Time to onset of CDI events on T25FWT, defined as ≥ 20% decrease on the T25FWT score from baseline, confirmed over at least 24 weeks

  8. Symbol Digit Modalities Test

    Timeframe: Up to approximately 120 weeks

    The change in cognitive function as assessed by Symbol Digit Modalities Test (SDMT) from baseline to each scheduled visit

  9. Annualized relapse rate

    Timeframe: Up to approximately 120 weeks

    Annualized relapse rate (ARR) during the study period assessed by protocol-defined adjudicated relapses

  10. To evaluate the safety and tolerability of orelabrutinib

    Timeframe: 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);

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults
Minimum age
18 Years
Maximum age
60 Years
Healthy volunteers
No

  1. 18 to 60 years of age, inclusive, at the time of signing the informed consent.
  2. Participant must have a previous diagnosis of RRMS in accordance with 2024 McDonald criteria
  3. Participant must have a current diagnosis of SPMS in accordance with the clinical course criteria revised in 2013
  4. Participant must have documented evidence of disability progression independent of clinical relapse observed during the 24 months before screening. A written summary of the clinical evidence of disability progression must be discussed and aligned between the Investigator and the Sponsor's dedicated qualified person(s).
  5. Absence of clinical relapses for at least 24 months.

  1. The patient has been diagnosed with primary progressive MS (PPMS) according to 2024 McDonald diagnostic criteria
  2. Immunologic disorder other than MS or any other conditions requiring corticosteroid therapy.
  3. History or current diagnosis of other neurological disorders that may mimic MS
  4. History or current diagnosis of progressive multifocal leukoencephalopathy
  5. Active, clinically significant viral, bacterial, or fungal infection
  6. History of any other significant active medical condition
  7. History of suicidal behavior within 6 months prior to Screening
  8. Any prior history of malignancy
  9. Patients on anticoagulation, or antiplatelet therapy
  10. Patients took strong/moderate CYP3A inhibitors or strong/moderate CYP3A inducers within 14 days
  11. Clinically significant laboratory abnormalities at Screening.
  12. Vaccination with live or live-attenuated virus vaccine within 1 month prior to Screening
  13. History of alcohol abuse or alcohol use disorder or other drug abuse within 12 months prior to screening.
Sources for eligibility
clinicaltrials.gov

  • Arizona Neuroscience Research, LLCPhoenix, United StatesRecruiting
  • Perseverance Research Center, LLC (PRC)Scottsdale, United StatesRecruiting
  • Fullerton Neurology and Headache CenterFullerton, United StatesRecruiting
  • Harbor-UCLA Medical Center - The Lundquist Institute (Los Angeles Biomedical Research Institute (LA BioMed))Torrance, United StatesRecruiting
  • Regina Berkovich MD, PhD IncWest Hollywood, United StatesRecruiting
  • SFM Clinical Research, LLCBoca Raton, United StatesRecruiting
  • Nova Clinical Research, LLCBradenton, United StatesRecruiting
  • MS and Neuromuscular Center of ExcellenceClearwater, United StatesRecruiting
  • Neurology AssociatesMaitland, United StatesRecruiting
  • Aqualane Clinical ResearchNaples, United StatesRecruiting
  • University of South Florida Department of Neurology - MS DivisionTampa, United StatesRecruiting
  • Josephson Wallack Munshower Neurology, Pc Suite 225Indianapolis, United StatesRecruiting
  • KC Research Center, PA Neurology Research DeptRoeland Park, United StatesRecruiting
  • Boston Clinical TrialsBoston, United StatesWithdrawn
  • University of Massachusetts Memorial Medical CenterWorcester, United StatesRecruiting
  • Profound Research LLC at Oakland Neurology CenterRochester Hills, United StatesRecruiting
  • Washington University School of MedicineSt Louis, United StatesRecruiting
  • University Of New Mexico School Of MedicineAlbuquerque, United StatesRecruiting
  • Mount Sinai Medical CenterNew York, United StatesRecruiting
  • The Ohio State University Wexner Medical Center (OSUWMC)Columbus, United StatesRecruiting
  • The Boster Center for Multiple SclerosisColumbus, United StatesRecruiting
  • OMRF Multiple Sclerosis Center of ExcellenceOklahoma City, United StatesRecruiting
  • Premier NeurologyGreenville, United StatesRecruiting
  • Neurology Clinic, P.C.Cordova, United StatesRecruiting
  • Lone Star NeurologySan Antonio, United StatesRecruiting

And 44 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (2)

Targets (1)